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image of Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy

Abstract

Pericytes, also known as mural cells, are cells embedded between endothelial cells and the basement membrane of capillaries, where they orchestrate the morphological and functional homeostasis of blood vessels. Within the tumor microenvironment, pericytes interact closely with various cellular components, including tumor cells, stromal cells, and immune cells. Through these dynamic interactions, pericytes are activated and subsequently transform into tumor-associated pericytes (TPCs). The origin of TPCs varies depending on the tissue and tumor type, contributing to their phenotypic and functional heterogeneity. TPCs play pivotal roles in facilitating tumor progression, metastasis, immune evasion, and therapeutic resistance by promoting angiogenesis, engaging in reciprocal interactions with tumor cells, remodeling the extracellular matrix, and fostering an immunosuppressive microenvironment. This review synthesizes the latest significant advancements in targeted therapies against TPCs. It underscores the challenges inherent in developing effective anti-TPC therapies, which include the heterogeneity and pluripotency of TPCs, the absence of specific markers for precise TPC targeting, and the limited understanding of how current anti-tumor therapies affect TPCs and vice versa. This review furnishes a comprehensive understanding of the origins, markers, and functions of TPCs, and their interplays within the tumor microenvironment, providing prospective strategies for more effective anti-tumor therapy.

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/content/journals/cvp/10.2174/0115701611365339250213101338
2025-02-19
2025-04-15
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References

  1. de Visser K.E. Joyce J.A. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell 2023 41 3 374 403 10.1016/j.ccell.2023.02.016 36917948
    [Google Scholar]
  2. Bejarano L. Jordāo M.J.C. Joyce J.A. Therapeutic targeting of the tumor microenvironment. Cancer Discov. 2021 11 4 933 959 10.1158/2159‑8290.CD‑20‑1808 33811125
    [Google Scholar]
  3. Jiang Z. Zhou J. Li L. Liao S. He J. Zhou S. Zhou Y. Pericytes in the tumor microenvironment. Cancer Lett. 2023 556 216074 10.1016/j.canlet.2023.216074 36682706
    [Google Scholar]
  4. Hanahan D. Hallmarks of cancer: New dimensions. Cancer Discov. 2022 12 1 31 46 10.1158/2159‑8290.CD‑21‑1059 35022204
    [Google Scholar]
  5. Chung A.S. Lee J. Ferrara N. Targeting the tumour vasculature: Insights from physiological angiogenesis. Nat. Rev. Cancer 2010 10 7 505 514 10.1038/nrc2868 20574450
    [Google Scholar]
  6. Eelen G. Treps L. Li X. Carmeliet P. Basic and therapeutic aspects of angiogenesis updated. Circ. Res. 2020 127 2 310 329 10.1161/CIRCRESAHA.120.316851 32833569
    [Google Scholar]
  7. Holm A. Heumann T. Augustin H.G. Microvascular mural cell organotypic heterogeneity and functional plasticity. Trends Cell Biol. 2018 28 4 302 316 10.1016/j.tcb.2017.12.002 29307447
    [Google Scholar]
  8. Armulik A. Genové G. Betsholtz C. Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 2011 21 2 193 215 10.1016/j.devcel.2011.07.001 21839917
    [Google Scholar]
  9. Hellström M. Gerhardt H. Kalén M. Li X. Eriksson U. Wolburg H. Betsholtz C. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol. 2001 153 3 543 554 10.1083/jcb.153.3.543 11331305
    [Google Scholar]
  10. Enge M. Bjarnegård M. Gerhardt H. Gustafsson E. Kalén M. Asker N. Hammes H.P. Shani M. Fässler R. Betsholtz C. Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J. 2002 21 16 4307 4316 10.1093/emboj/cdf418 12169633
    [Google Scholar]
  11. Li X. Pan J. Liu T. Yin W. Miao Q. Zhao Z. Gao Y. Zheng W. Li H. Deng R. Huang D. Qiu S. Zhang Y. Qi Q. Deng L. Huang M. Tang P.M.K. Cao Y. Chen M. Ye W. Zhang D. Novel TCF21 high pericyte subpopulation promotes colorectal cancer metastasis by remodelling perivascular matrix. Gut 2023 72 4 710 721 10.1136/gutjnl‑2022‑327913 36805487
    [Google Scholar]
  12. Li X. Qi Q. Li Y. Miao Q. Yin W. Pan J. Zhao Z. Chen X. Yang F. Zhou X. Huang M. Wang C. Deng L. Huang D. Qi M. Fan S. Zhang Y. Qiu S. Deng W. Liu T. Chen M. Ye W. Zhang D. TCAF2 in pericytes promotes colorectal cancer liver metastasis via inhibiting cold‐sensing TRPM8 channel. Adv. Sci. 2023 10 30 2302717 10.1002/advs.202302717 37635201
    [Google Scholar]
  13. Zhang C. Du Z. Gao Y. Lim K.S. Zhou W. Huang H. He H. Xiao J. Xu D. Li Q. Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma. Cell Metab. 2024 36 4 778 792.e10 10.1016/j.cmet.2024.01.018 38378000
    [Google Scholar]
  14. Hirz T. Mei S. Sarkar H. Kfoury Y. Wu S. Verhoeven B.M. Subtelny A.O. Zlatev D.V. Wszolek M.W. Salari K. Murray E. Chen F. Macosko E.Z. Wu C.L. Scadden D.T. Dahl D.M. Baryawno N. Saylor P.J. Kharchenko P.V. Sykes D.B. Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses. Nat. Commun. 2023 14 1 663 10.1038/s41467‑023‑36325‑2 36750562
    [Google Scholar]
  15. Huang M. Chen M. Qi M. Ye G. Pan J. Shi C. Yang Y. Zhao L. Mo X. Zhang Y. Li Y. Zhong J. Lu W. Li X. Zhang J. Lin J. Luo L. Liu T. Tang P.M.K. Hong A. Cao Y. Ye W. Zhang D. Perivascular cell‐derived extracellular vesicles stimulate colorectal cancer revascularization after withdrawal of antiangiogenic drugs. J. Extracell. Vesicles 2021 10 7 e12096 10.1002/jev2.12096 34035882
    [Google Scholar]
  16. Huang M. Liu M. Huang D. Ma Y. Ye G. Wen Q. Li Y. Deng L. Qi Q. Liu T. Liu X. Chen M. Ye W. Zhang D. Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway. Cancer Lett. 2022 524 131 143 10.1016/j.canlet.2021.10.023 34678434
    [Google Scholar]
  17. Wong P.P. Muñoz-Félix J.M. Hijazi M. Kim H. Robinson S.D. De Luxán-Delgado B. Rodríguez-Hernández I. Maiques O. Meng Y.M. Meng Q. Bodrug N. Dukinfield M.S. Reynolds L.E. Elia G. Clear A. Harwood C. Wang Y. Campbell J.J. Singh R. Zhang P. Schall T.J. Matchett K.P. Henderson N.C. Szlosarek P.W. Dreger S.A. Smith S. Jones J.L. Gribben J.G. Cutillas P.R. Meier P. Sanz-Moreno V. Hodivala-Dilke K.M. Cancer burden is controlled by mural cell-β3-Integrin regulated crosstalk with tumor cells. Cell 2020 181 6 1346 1363.e21 10.1016/j.cell.2020.02.003 32473126
    [Google Scholar]
  18. Wang Y. Sun Q. Ye Y. Sun X. Xie S. Zhan Y. Song J. Fan X. Zhang B. Yang M. Lv L. Hosaka K. Yang Y. Nie G. FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis. JCI Insight 2022 7 10 e157874 10.1172/jci.insight.157874 35439170
    [Google Scholar]
  19. Hamzah J. Jugold M. Kiessling F. Rigby P. Manzur M. Marti H.H. Rabie T. Kaden S. Gröne H.J. Hämmerling G.J. Arnold B. Ganss R. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature 2008 453 7193 410 414 10.1038/nature06868 18418378
    [Google Scholar]
  20. Zhang X.N. Yang K.D. Chen C. He Z.C. Wang Q.H. Feng H. Lv S.Q. Wang Y. Mao M. Liu Q. Tan Y.Y. Wang W.Y. Li T.R. Che L.R. Qin Z.Y. Wu L.X. Luo M. Luo C.H. Liu Y.Q. Yin W. Wang C. Guo H.T. Li Q.R. Wang B. Chen W. Wang S. Shi Y. Bian X.W. Ping Y.F. Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling. Cell Res. 2021 31 10 1072 1087 10.1038/s41422‑021‑00528‑3 34239070
    [Google Scholar]
  21. Murgai M. Ju W. Eason M. Kline J. Beury D.W. Kaczanowska S. Miettinen M.M. Kruhlak M. Lei H. Shern J.F. Cherepanova O.A. Owens G.K. Kaplan R.N. KLF4-dependent perivascular cell plasticity mediates pre-metastatic niche formation and metastasis. Nat. Med. 2017 23 10 1176 1190 10.1038/nm.4400 28920957
    [Google Scholar]
  22. Qi M. Fan S. Huang M. Pan J. Li Y. Miao Q. Lyu W. Li X. Deng L. Qiu S. Liu T. Deng W. Chu X. Jiang C. He W. Xia L. Yang Y. Hong J. Qi Q. Yin W. Liu X. Shi C. Chen M. Ye W. Zhang D. Targeting FAPα-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models. J. Clin. Invest. 2022 132 19 e157399 10.1172/JCI157399 35951441
    [Google Scholar]
  23. Huang Q. Liu L. Xiao D. Huang Z. Wang W. Zhai K. Fang X. Kim J. Liu J. Liang W. He J. Bao S. CD44+ lung cancer stem cell-derived pericyte-like cells cause brain metastases through GPR124-enhanced trans-endothelial migration. Cancer Cell 2023 41 9 1621 1636.e8 10.1016/j.ccell.2023.07.012 37595587
    [Google Scholar]
  24. Foster K. Sheridan J. Veiga-Fernandes H. Roderick K. Pachnis V. Adams R. Blackburn C. Kioussis D. Coles M. Contribution of neural crest-derived cells in the embryonic and adult thymus. J. Immunol. 2008 180 5 3183 3189 10.4049/jimmunol.180.5.3183 18292542
    [Google Scholar]
  25. Heglind M. Cederberg A. Aquino J. Lucas G. Ernfors P. Enerbäck S. Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight. Mol. Cell. Biol. 2005 25 13 5616 5625 10.1128/MCB.25.13.5616‑5625.2005 15964817
    [Google Scholar]
  26. Trost A. Schroedl F. Lange S. Rivera F.J. Tempfer H. Korntner S. Stolt C.C. Wegner M. Bogner B. Kaser-Eichberger A. Krefft K. Runge C. Aigner L. Reitsamer H.A. Neural crest origin of retinal and choroidal pericytes. Invest. Ophthalmol. Vis. Sci. 2013 54 13 7910 7921 10.1167/iovs.13‑12946 24235018
    [Google Scholar]
  27. Que J. Wilm B. Hasegawa H. Wang F. Bader D. Hogan B.L.M. Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development. Proc. Natl. Acad. Sci. USA 2008 105 43 16626 16630 10.1073/pnas.0808649105 18922767
    [Google Scholar]
  28. Wilm B. Ipenberg A. Hastie N.D. Burch J.B.E. Bader D.M. The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development 2005 132 23 5317 5328 10.1242/dev.02141 16284122
    [Google Scholar]
  29. Asahina K. Zhou B. Pu W.T. Tsukamoto H. Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver. Hepatology 2011 53 3 983 995 10.1002/hep.24119 21294146
    [Google Scholar]
  30. Bababeygy S.R. Cheshier S.H. Hou L.C. Higgins D.M.O. Weissman I.L. Tse V.C.K. Hematopoietic stem cell-derived pericytic cells in brain tumor angio-architecture. Stem Cells Dev. 2008 17 1 11 18 10.1089/scd.2007.0117 18240955
    [Google Scholar]
  31. Birbrair A. Zhang T. Wang Z.M. Messi M.L. Mintz A. Delbono O. Pericytes: multitasking cells in the regeneration of injured, diseased, and aged skeletal muscle. Front. Aging Neurosci. 2014 6 245 10.3389/fnagi.2014.00245 25278877
    [Google Scholar]
  32. Hosaka K. Yang Y. Seki T. Fischer C. Dubey O. Fredlund E. Hartman J. Religa P. Morikawa H. Ishii Y. Sasahara M. Larsson O. Cossu G. Cao R. Lim S. Cao Y. Pericyte–fibroblast transition promotes tumor growth and metastasis. Proc. Natl. Acad. Sci. USA 2016 113 38 E5618 E5627 10.1073/pnas.1608384113 27608497
    [Google Scholar]
  33. Stratman A.N. Schwindt A.E. Malotte K.M. Davis G.E. Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization. Blood 2010 116 22 4720 4730 10.1182/blood‑2010‑05‑286872 20739660
    [Google Scholar]
  34. Yu Y. Leng Y. Song X. Mu J. Ma L. Yin L. Zheng Y. Lu Y. Li Y. Qiu X. Zhu H. Li J. Wang D. Extracellular matrix stiffness regulates microvascular stability by controlling endothelial paracrine signaling to determine pericyte fate. Arterioscler. Thromb. Vasc. Biol. 2023 43 10 1887 1899 10.1161/ATVBAHA.123.319119 37650330
    [Google Scholar]
  35. Minutti C.M. Modak R.V. Macdonald F. Li F. Smyth D.J. Dorward D.A. Blair N. Husovsky C. Muir A. Giampazolias E. Dobie R. Maizels R.M. Kendall T.J. Griggs D.W. Kopf M. Henderson N.C. Zaiss D.M. A macrophage-pericyte axis directs tissue restoration via amphiregulin-induced transforming growth factor beta activation. Immunity 2019 50 3 645 654.e6 10.1016/j.immuni.2019.01.008 30770250
    [Google Scholar]
  36. Diéguez-Hurtado R. Kato K. Giaimo B.D. Nieminen-Kelhä M. Arf H. Ferrante F. Bartkuhn M. Zimmermann T. Bixel M.G. Eilken H.M. Adams S. Borggrefe T. Vajkoczy P. Adams R.H. Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes. Nat. Commun. 2019 10 1 2817 10.1038/s41467‑019‑10643‑w 31249304
    [Google Scholar]
  37. Machuca-Parra A.I. Bigger-Allen A.A. Sanchez A.V. Boutabla A. Cardona-Vélez J. Amarnani D. Saint-Geniez M. Siebel C.W. Kim L.A. D’Amore P.A. Arboleda-Velasquez J.F. Therapeutic antibody targeting of Notch3 signaling prevents mural cell loss in CADASIL. J. Exp. Med. 2017 214 8 2271 2282 10.1084/jem.20161715 28698285
    [Google Scholar]
  38. Jin S. Hansson E.M. Tikka S. Lanner F. Sahlgren C. Farnebo F. Baumann M. Kalimo H. Lendahl U. Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells. Circ. Res. 2008 102 12 1483 1491 10.1161/CIRCRESAHA.107.167965 18483410
    [Google Scholar]
  39. van Splunder H. Villacampa P. Martínez-Romero A. Graupera M. Pericytes in the disease spotlight. Trends Cell Biol. 2024 34 1 58 71 10.1016/j.tcb.2023.06.001 37474376
    [Google Scholar]
  40. Meng Y.M. Jiang X. Zhao X. Meng Q. Wu S. Chen Y. Kong X. Qiu X. Su L. Huang C. Wang M. Liu C. Wong P.P. Hexokinase 2-driven glycolysis in pericytes activates their contractility leading to tumor blood vessel abnormalities. Nat. Commun. 2021 12 1 6011 10.1038/s41467‑021‑26259‑y 34650057
    [Google Scholar]
  41. Kuppe C. Ibrahim M.M. Kranz J. Zhang X. Ziegler S. Perales-Patón J. Jansen J. Reimer K.C. Smith J.R. Dobie R. Wilson-Kanamori J.R. Halder M. Xu Y. Kabgani N. Kaesler N. Klaus M. Gernhold L. Puelles V.G. Huber T.B. Boor P. Menzel S. Hoogenboezem R.M. Bindels E.M.J. Steffens J. Floege J. Schneider R.K. Saez-Rodriguez J. Henderson N.C. Kramann R. Decoding myofibroblast origins in human kidney fibrosis. Nature 2021 589 7841 281 286 10.1038/s41586‑020‑2941‑1 33176333
    [Google Scholar]
  42. Yang A.C. Vest R.T. Kern F. Lee D.P. Agam M. Maat C.A. Losada P.M. Chen M.B. Schaum N. Khoury N. Toland A. Calcuttawala K. Shin H. Pálovics R. Shin A. Wang E.Y. Luo J. Gate D. Schulz-Schaeffer W.J. Chu P. Siegenthaler J.A. McNerney M.W. Keller A. Wyss-Coray T. A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk. Nature 2022 603 7903 885 892 10.1038/s41586‑021‑04369‑3 35165441
    [Google Scholar]
  43. Vanlandewijck M. He L. Mäe M.A. Andrae J. Ando K. Del Gaudio F. Nahar K. Lebouvier T. Laviña B. Gouveia L. Sun Y. Raschperger E. Räsänen M. Zarb Y. Mochizuki N. Keller A. Lendahl U. Betsholtz C. A molecular atlas of cell types and zonation in the brain vasculature. Nature 2018 554 7693 475 480 10.1038/nature25739 29443965
    [Google Scholar]
  44. Muhl L. Genové G. Leptidis S. Liu J. He L. Mocci G. Sun Y. Gustafsson S. Buyandelger B. Chivukula I.V. Segerstolpe Å. Raschperger E. Hansson E.M. Björkegren J.L.M. Peng X.R. Vanlandewijck M. Lendahl U. Betsholtz C. Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination. Nat. Commun. 2020 11 1 3953 10.1038/s41467‑020‑17740‑1 32769974
    [Google Scholar]
  45. Muhl L. Mocci G. Pietilä R. Liu J. He L. Genové G. Leptidis S. Gustafsson S. Buyandelger B. Raschperger E. Hansson E.M. Björkegren J.L.M. Vanlandewijck M. Lendahl U. Betsholtz C. A single-cell transcriptomic inventory of murine smooth muscle cells. Dev. Cell 2022 57 20 2426 2443.e6 10.1016/j.devcel.2022.09.015 36283392
    [Google Scholar]
  46. Shih Y.H. Portman D. Idrizi F. Grosse A. Lawson N.D. Integrated molecular analysis identifies a conserved pericyte gene signature in zebrafish. Development 2021 148 23 dev200189 10.1242/dev.200189 34751773
    [Google Scholar]
  47. Glabman R.A. Choyke P.L. Sato N. Cancer-associated fibroblasts: Tumorigenicity and targeting for cancer therapy. Cancers 2022 14 16 3906 10.3390/cancers14163906 36010899
    [Google Scholar]
  48. Du Y. Shi J. Wang J. Xun Z. Yu Z. Sun H. Bao R. Zheng J. Li Z. Ye Y. Integration of pan-cancer single-cell and spatial transcriptomics reveals stromal cell features and therapeutic targets in tumor microenvironment. Cancer Res. 2024 84 2 192 210 10.1158/0008‑5472.CAN‑23‑1418 38225927
    [Google Scholar]
  49. Sziraki A. Zhong Y. Neltner A.M. Niedowicz D.M. Rogers C.B. Wilcock D.M. Nehra G. Neltner J.H. Smith R.R. Hartz A.M. Cao J. Nelson P.T. A high‐throughput single‐cell RNA expression profiling method identifies human pericyte markers. Neuropathol. Appl. Neurobiol. 2023 49 6 e12942 10.1111/nan.12942 37812061
    [Google Scholar]
  50. Crisan M. Yap S. Casteilla L. Chen C.W. Corselli M. Park T.S. Andriolo G. Sun B. Zheng B. Zhang L. Norotte C. Teng P.N. Traas J. Schugar R. Deasy B.M. Badylak S. Bűhring H.J. Giacobino J.P. Lazzari L. Huard J. Péault B. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008 3 3 301 313 10.1016/j.stem.2008.07.003 18786417
    [Google Scholar]
  51. Ozerdem U. Grako K.A. Dahlin-Huppe K. Monosov E. Stallcup W.B. NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev. Dyn. 2001 222 2 218 227 10.1002/dvdy.1200 11668599
    [Google Scholar]
  52. Liu Y. Guo J. Matoga M. Korotkova M. Jakobsson P.J. Aguzzi A. NG2 glia protect against prion neurotoxicity by inhibiting microglia-to-neuron prostaglandin E2 signaling. Nat. Neurosci. 2024 27 8 1534 1544 10.1038/s41593‑024‑01663‑x 38802591
    [Google Scholar]
  53. Smyth L.C.D. Rustenhoven J. Scotter E.L. Schweder P. Faull R.L.M. Park T.I.H. Dragunow M. Markers for human brain pericytes and smooth muscle cells. J. Chem. Neuroanat. 2018 92 48 60 10.1016/j.jchemneu.2018.06.001 29885791
    [Google Scholar]
  54. Zhu S. Chen M. Ying Y. Wu Q. Huang Z. Ni W. Wang X. Xu H. Bennett S. Xiao J. Xu J. Versatile subtypes of pericytes and their roles in spinal cord injury repair, bone development and repair. Bone Res. 2022 10 1 30 10.1038/s41413‑022‑00203‑2 35296645
    [Google Scholar]
  55. Zimmerlin L. Donnenberg V.S. Rubin J.P. Donnenberg A.D. Mesenchymal markers on human adipose stem/progenitor cells. Cytometry A 2013 83A 1 134 140 10.1002/cyto.a.22227 23184564
    [Google Scholar]
  56. Xing S. Luo Y. Liu Z. Bu P. Duan H. Liu D. Wang P. Yang J. Song L. Feng J. Yang D. Qin Z. Yan X. Targeting endothelial CD146 attenuates colitis and prevents colitis-associated carcinogenesis. Am. J. Pathol. 2014 184 5 1604 1616 10.1016/j.ajpath.2014.01.031 24767106
    [Google Scholar]
  57. Dagur P.K. McCoy J.P. Jr Endothelial-binding, proinflammatory T cells identified by MCAM (CD146) expression: Characterization and role in human autoimmune diseases. Autoimmun. Rev. 2015 14 5 415 422 10.1016/j.autrev.2015.01.003 25595133
    [Google Scholar]
  58. Zhang H. Bryson V.G. Wang C. Li T. Kerr J.P. Wilson R. Muoio D.M. Bloch R.J. Ward C. Rosenberg P.B. Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle. JCI Insight 2021 6 17 e143472 10.1172/jci.insight.143472 34494555
    [Google Scholar]
  59. Hong C.L. Yu I.S. Pai C.H. Chen J.S. Hsieh M.S. Wu H.L. Lin S.W. Huang H.P. CD248 regulates Wnt signaling in pericytes to promote angiogenesis and tumor growth in lung cancer. Cancer Res. 2022 82 20 3734 3750 10.1158/0008‑5472.CAN‑22‑1695 35950912
    [Google Scholar]
  60. Ash S.L. Orha R. Mole H. Dinesh-Kumar M. Lee S.P. Turrell F.K. Isacke C.M. Targeting the activated microenvironment with endosialin (CD248)-directed CAR-T cells ablates perivascular cells to impair tumor growth and metastasis. J. Immunother. Cancer 2024 12 2 e008608 10.1136/jitc‑2023‑008608 38413223
    [Google Scholar]
  61. Kim H.S. Choi D.Y. Yun S.J. Choi S.M. Kang J.W. Jung J.W. Hwang D. Kim K.P. Kim D.W. Proteomic analysis of microvesicles derived from human mesenchymal stem cells. J. Proteome Res. 2012 11 2 839 849 10.1021/pr200682z 22148876
    [Google Scholar]
  62. Kontsekova S Polcicova K Takacova M Pastorekova S. Molecular and functional links to tumor Angiogenesis. Neoplasma 2016 63 2 183 192 10.4149/202_15090N474
    [Google Scholar]
  63. Cho H. Kozasa T. Bondjers C. Betsholtz C. Kehrl J.H. Pericyte‐specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J. 2003 17 3 1 17 10.1096/fj.02‑0340fje 12514120
    [Google Scholar]
  64. Kong P. Wang X. Gao Y.K. Zhang D.D. Huang X.F. Song Y. Zhang W.D. Guo R.J. Li H. Han M. RGS5 maintaining vascular homeostasis is altered by the tumor microenvironment. Biol. Direct 2023 18 1 78 10.1186/s13062‑023‑00437‑y 37986113
    [Google Scholar]
  65. Song S. Ewald A.J. Stallcup W. Werb Z. Bergers G. PDGFRβ+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat. Cell Biol. 2005 7 9 870 879 10.1038/ncb1288 16113679
    [Google Scholar]
  66. Costa A. Kieffer Y. Scholer-Dahirel A. Pelon F. Bourachot B. Cardon M. Sirven P. Magagna I. Fuhrmann L. Bernard C. Bonneau C. Kondratova M. Kuperstein I. Zinovyev A. Givel A.M. Parrini M.C. Soumelis V. Vincent-Salomon A. Mechta-Grigoriou F. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell 2018 33 3 463 479.e10 10.1016/j.ccell.2018.01.011 29455927
    [Google Scholar]
  67. Nurmik M. Ullmann P. Rodriguez F. Haan S. Letellier E. In search of definitions: Cancer‐associated fibroblasts and their markers. Int. J. Cancer 2020 146 4 895 905 10.1002/ijc.32193 30734283
    [Google Scholar]
  68. Sugimoto H. Mundel T.M. Kieran M.W. Kalluri R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol. Ther. 2006 5 12 1640 1646 10.4161/cbt.5.12.3354 17106243
    [Google Scholar]
  69. Dar A. Domev H. Ben-Yosef O. Tzukerman M. Zeevi-Levin N. Novak A. Germanguz I. Amit M. Itskovitz-Eldor J. Multipotent vasculogenic pericytes from human pluripotent stem cells promote recovery of murine ischemic limb. Circulation 2012 125 1 87 99 10.1161/CIRCULATIONAHA.111.048264 22095829
    [Google Scholar]
  70. Mesa-Ciller C. Turiel G. Guajardo-Grence A. Lopez-Rodriguez A.B. Egea J. De Bock K. Aragonés J. Urrutia A.A. Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia. J. Cereb. Blood Flow Metab. 2023 43 1 44 58 10.1177/0271678X221118236 35929074
    [Google Scholar]
  71. Cords L. Tietscher S. Anzeneder T. Langwieder C. Rees M. de Souza N. Bodenmiller B. Cancer-associated fibroblast classification in single-cell and spatial proteomics data. Nat. Commun. 2023 14 1 4294 10.1038/s41467‑023‑39762‑1 37463917
    [Google Scholar]
  72. Chen Z. Wei X. Wang X. Zheng X. Chang B. Shen L. Zhu H. Yang M. Li S. Zheng X. NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib. Cell Death Dis. 2021 12 4 377 10.1038/s41419‑021‑03646‑3 33828084
    [Google Scholar]
  73. Ji H. Li Y. Sun H. Chen R. Zhou R. Yang Y. Wang R. You C. Xiao A. Yi L. Decoding the cell atlas and inflammatory features of human intracranial Aneurysm wall by single‐cell RNA sequencing. J. Am. Heart Assoc. 2024 13 5 e032456 10.1161/JAHA.123.032456 38390814
    [Google Scholar]
  74. Wang S. Zhang S. Li X. Li X. Zhao S. Guo J. Wang S. Wang R. Zhang M. Qiu W. HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients. Front. Immunol. 2024 15 1415148 10.3389/fimmu.2024.1415148 39108265
    [Google Scholar]
  75. Ando K. Tong L. Peng D. Vázquez-Liébanas E. Chiyoda H. He L. Liu J. Kawakami K. Mochizuki N. Fukuhara S. Grutzendler J. Betsholtz C. KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling. Dev. Cell 2022 57 11 1383 1399.e7 10.1016/j.devcel.2022.04.019 35588738
    [Google Scholar]
  76. Pan X. Li X. Dong L. Liu T. Zhang M. Zhang L. Zhang X. Huang L. Shi W. Sun H. Fang Z. Sun J. Huang Y. Shao H. Wang Y. Yin M. Tumour vasculature at single-cell resolution. Nature 2024 632 8024 429 436 10.1038/s41586‑024‑07698‑1 38987599
    [Google Scholar]
  77. Hoogstrate Y. Draaisma K. Ghisai S.A. van Hijfte L. Barin N. de Heer I. Coppieters W. van den Bosch T.P.P. Bolleboom A. Gao Z. Vincent A.J.P.E. Karim L. Deckers M. Taphoorn M.J.B. Kerkhof M. Weyerbrock A. Sanson M. Hoeben A. Lukacova S. Lombardi G. Leenstra S. Hanse M. Fleischeuer R.E.M. Watts C. Angelopoulos N. Gorlia T. Golfinopoulos V. Bours V. van den Bent M.J. Robe P.A. French P.J. Transcriptome analysis reveals tumor microenvironment changes in glioblastoma. Cancer Cell 2023 41 4 678 692.e7 10.1016/j.ccell.2023.02.019 36898379
    [Google Scholar]
  78. Teuwen L.A. De Rooij L.P.M.H. Cuypers A. Rohlenova K. Dumas S.J. García-Caballero M. Meta E. Amersfoort J. Taverna F. Becker L.M. Veiga N. Cantelmo A.R. Geldhof V. Conchinha N.V. Kalucka J. Treps L. Conradi L.C. Khan S. Karakach T.K. Soenen S. Vinckier S. Schoonjans L. Eelen G. Van Laere S. Dewerchin M. Dirix L. Mazzone M. Luo Y. Vermeulen P. Carmeliet P. Tumor vessel co-option probed by single-cell analysis. Cell Rep. 2021 35 11 109253 10.1016/j.celrep.2021.109253 34133923
    [Google Scholar]
  79. Feng F. Feng X. Zhang D. Li Q. Yao L. Matrix stiffness induces pericyte-fibroblast transition through YAP activation. Front. Pharmacol. 2021 12 698275 10.3389/fphar.2021.698275 34135765
    [Google Scholar]
  80. Ferland-McCollough D. Slater S. Richard J. Reni C. Mangialardi G. Pericytes, an overlooked player in vascular pathobiology. Pharmacol. Ther. 2017 171 30 42 10.1016/j.pharmthera.2016.11.008 27916653
    [Google Scholar]
  81. Perrot C.Y. Herrera J.L. Fournier-Goss A.E. Komatsu M. Prostaglandin E2 breaks down pericyte–endothelial cell interaction via EP1 and EP4-dependent downregulation of pericyte N-cadherin, connexin-43, and R-Ras. Sci. Rep. 2020 10 1 11186 10.1038/s41598‑020‑68019‑w 32636414
    [Google Scholar]
  82. Zhang X. Ren L. Wu J. Feng R. Chen Y. Li R. Wu M. Zheng M. Wu X.G. Luo W. He H. Huang Y. Tang M. Li J. ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42. J. Exp. Clin. Cancer Res. 2022 41 1 230 10.1186/s13046‑022‑02441‑y 35869555
    [Google Scholar]
  83. Kemp S.S. Aguera K.N. Cha B. Davis G.E. Defining endothelial cell-derived factors that promote pericyte recruitment and capillary network assembly. Arterioscler. Thromb. Vasc. Biol. 2020 40 11 2632 2648 10.1161/ATVBAHA.120.314948 32814441
    [Google Scholar]
  84. Dubrac A. Künzel S.E. Künzel S.H. Li J. Chandran R.R. Martin K. Greif D.M. Adams R.H. Eichmann A. NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy. Nat. Commun. 2018 9 1 3463 10.1038/s41467‑018‑05926‑7 30150707
    [Google Scholar]
  85. Darland D.C. Massingham L.J. Smith S.R. Piek E. Saint-Geniez M. D’Amore P.A. Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival. Dev. Biol. 2003 264 1 275 288 10.1016/j.ydbio.2003.08.015 14623248
    [Google Scholar]
  86. Ichikawa K. Watanabe Miyano S. Minoshima Y. Matsui J. Funahashi Y. Activated FGF2 signaling pathway in tumor vasculature is essential for acquired resistance to anti-VEGF therapy. Sci. Rep. 2020 10 1 2939 10.1038/s41598‑020‑59853‑z 32076044
    [Google Scholar]
  87. Franco M. Roswall P. Cortez E. Hanahan D. Pietras K. Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression. Blood 2011 118 10 2906 2917 10.1182/blood‑2011‑01‑331694 21778339
    [Google Scholar]
  88. Claesson-Welsh L. Welsh M. VEGFA and tumour angiogenesis. J. Intern. Med. 2013 273 2 114 127 10.1111/joim.12019 23216836
    [Google Scholar]
  89. Huang M. Lin Y. Wang C. Deng L. Chen M. Assaraf Y.G. Chen Z.S. Ye W. Zhang D. New insights into antiangiogenic therapy resistance in cancer: Mechanisms and therapeutic aspects. Drug Resist. Updat. 2022 64 100849 10.1016/j.drup.2022.100849 35842983
    [Google Scholar]
  90. Helfrich I. Scheffrahn I. Bartling S. Weis J. von Felbert V. Middleton M. Kato M. Ergün S. Augustin H.G. Schadendorf D. Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma. J. Exp. Med. 2010 207 3 491 503 10.1084/jem.20091846 20194633
    [Google Scholar]
  91. Cascone T. Herynk M.H. Xu L. Du Z. Kadara H. Nilsson M.B. Oborn C.J. Park Y.Y. Erez B. Jacoby J.J. Lee J.S. Lin H.Y. Ciardiello F. Herbst R.S. Langley R.R. Heymach J.V. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma. J. Clin. Invest. 2011 121 4 1313 1328 10.1172/JCI42405 21436589
    [Google Scholar]
  92. Okamoto S. Nitta M. Maruyama T. Sawada T. Komori T. Okada Y. Muragaki Y. Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas. Brain Tumor Pathol. 2016 33 2 129 136 10.1007/s10014‑016‑0248‑6 26826105
    [Google Scholar]
  93. Prete A. Lo A.S. Sadow P.M. Bhasin S.S. Antonello Z.A. Vodopivec D.M. Ullas S. Sims J.N. Clohessy J. Dvorak A.M. Sciuto T. Bhasin M. Murphy-Ullrich J.E. Lawler J. Karumanchi S.A. Nucera C. Pericytes elicit resistance to vemurafenib and sorafenib therapy in thyroid carcinoma via the TSP-1/TGFβ1 axis. Clin. Cancer Res. 2018 24 23 6078 6097 10.1158/1078‑0432.CCR‑18‑0693 30076136
    [Google Scholar]
  94. Hainsworth J.D. Spigel D.R. Sosman J.A. Burris H.A. III Farley C. Cucullu H. Yost K. Hart L.L. Sylvester L. Waterhouse D.M. Greco F.A. Treatment of advanced renal cell carcinoma with the combination bevacizumab/erlotinib/imatinib: A phase I/II trial. Clin. Genitourin. Cancer 2007 5 7 427 432 10.3816/CGC.2007.n.030 18272024
    [Google Scholar]
  95. Niu N. Shen X. Wang Z. Chen Y. Weng Y. Yu F. Tang Y. Lu P. Liu M. Wang L. Sun Y. Yang M. Shen B. Jin J. Lu Z. Jiang K. Shi Y. Xue J. Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer. Cancer Cell 2024 42 5 869 884.e9 10.1016/j.ccell.2024.03.005 38579725
    [Google Scholar]
  96. Donahue K.L. Watkoske H.R. Kadiyala P. Du W. Brown K. Scales M.K. Elhossiny A.M. Espinoza C.E. Lasse Opsahl E.L. Griffith B.D. Wen Y. Sun L. Velez-Delgado A. Renollet N.M. Morales J. Nedzesky N.M. Baliira R.K. Menjivar R.E. Medina-Cabrera P.I. Rao A. Allen B. Shi J. Frankel T.L. Carpenter E.S. Bednar F. Zhang Y. Pasca di Magliano M. Oncogenic KRAS-dependent stromal interleukin-33 directs the pancreatic microenvironment to promote tumor growth. Cancer Discov. 2024 14 10 1964 1989 10.1158/2159‑8290.CD‑24‑0100 38958646
    [Google Scholar]
  97. Er E.E. Valiente M. Ganesh K. Zou Y. Agrawal S. Hu J. Griscom B. Rosenblum M. Boire A. Brogi E. Giancotti F.G. Schachner M. Malladi S. Massagué J. Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat. Cell Biol. 2018 20 8 966 978 10.1038/s41556‑018‑0138‑8 30038252
    [Google Scholar]
  98. Shenoy A.K. Jin Y. Luo H. Tang M. Pampo C. Shao R. Siemann D.W. Wu L. Heldermon C.D. Law B.K. Chang L.J. Lu J. Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells. J. Clin. Invest. 2016 126 11 4174 4186 10.1172/JCI86623 27721239
    [Google Scholar]
  99. Lu J. Shenoy A. Epithelial-to-pericyte transition in cancer. Cancers 2017 9 7 77 10.3390/cancers9070077 28677655
    [Google Scholar]
  100. Wirsik N.M. Ehlers J. Mäder L. Ilina E.I. Blank A.E. Grote A. Feuerhake F. Baumgarten P. Devraj K. Harter P.N. Mittelbronn M. Naumann U. TGF‐β activates pericytes via induction of the epithelial‐to‐mesenchymal transition protein SLUG in glioblastoma. Neuropathol. Appl. Neurobiol. 2021 47 6 768 780 10.1111/nan.12714 33780024
    [Google Scholar]
  101. James A.W. Hindle P. Murray I.R. West C.C. Tawonsawatruk T. Shen J. Asatrian G. Zhang X. Nguyen V. Simpson A.H. Ting K. Péault B. Soo C. Pericytes for the treatment of orthopedic conditions. Pharmacol. Ther. 2017 171 93 103 10.1016/j.pharmthera.2016.08.003 27510330
    [Google Scholar]
  102. Xu C. Hong Q. Zhuang K. Ren X. Cui S. Dong Z. Wang Q. Bai X. Chen X. Regulation of pericyte metabolic reprogramming restricts the AKI to CKD transition. Metabolism 2023 145 155592 10.1016/j.metabol.2023.155592 37230215
    [Google Scholar]
  103. Biffi G. Tuveson D.A. Diversity and biology of cancer-associated fibroblasts. Physiol. Rev. 2021 101 1 147 176 10.1152/physrev.00048.2019 32466724
    [Google Scholar]
  104. Leask A. Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ. Res. 2010 106 11 1675 1680 10.1161/CIRCRESAHA.110.217737 20538689
    [Google Scholar]
  105. Garon E.B. Rizvi N.A. Hui R. Leighl N. Balmanoukian A.S. Eder J.P. Patnaik A. Aggarwal C. Gubens M. Horn L. Carcereny E. Ahn M.J. Felip E. Lee J.S. Hellmann M.D. Hamid O. Goldman J.W. Soria J.C. Dolled-Filhart M. Rutledge R.Z. Zhang J. Lunceford J.K. Rangwala R. Lubiniecki G.M. Roach C. Emancipator K. Gandhi L. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 2015 372 21 2018 2028 10.1056/NEJMoa1501824 25891174
    [Google Scholar]
  106. Gandhi L. Rodríguez-Abreu D. Gadgeel S. Esteban E. Felip E. De Angelis F. Domine M. Clingan P. Hochmair M.J. Powell S.F. Cheng S.Y.S. Bischoff H.G. Peled N. Grossi F. Jennens R.R. Reck M. Hui R. Garon E.B. Boyer M. Rubio-Viqueira B. Novello S. Kurata T. Gray J.E. Vida J. Wei Z. Yang J. Raftopoulos H. Pietanza M.C. Garassino M.C. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N. Engl. J. Med. 2018 378 22 2078 2092 10.1056/NEJMoa1801005 29658856
    [Google Scholar]
  107. Hamid O. Robert C. Daud A. Hodi F.S. Hwu W.J. Kefford R. Wolchok J.D. Hersey P. Joseph R.W. Weber J.S. Dronca R. Gangadhar T.C. Patnaik A. Zarour H. Joshua A.M. Gergich K. Elassaiss-Schaap J. Algazi A. Mateus C. Boasberg P. Tumeh P.C. Chmielowski B. Ebbinghaus S.W. Li X.N. Kang S.P. Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 2013 369 2 134 144 10.1056/NEJMoa1305133 23724846
    [Google Scholar]
  108. Larkin J. Chiarion-Sileni V. Gonzalez R. Grob J.J. Rutkowski P. Lao C.D. Cowey C.L. Schadendorf D. Wagstaff J. Dummer R. Ferrucci P.F. Smylie M. Hogg D. Hill A. Márquez-Rodas I. Haanen J. Guidoboni M. Maio M. Schöffski P. Carlino M.S. Lebbé C. McArthur G. Ascierto P.A. Daniels G.A. Long G.V. Bastholt L. Rizzo J.I. Balogh A. Moshyk A. Hodi F.S. Wolchok J.D. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 2019 381 16 1535 1546 10.1056/NEJMoa1910836 31562797
    [Google Scholar]
  109. Pan Y. Yu Y. Wang X. Zhang T. Tumor-associated macrophages in tumor immunity. Front. Immunol. 2020 11 583084 10.3389/fimmu.2020.583084 33365025
    [Google Scholar]
  110. Wu K. Lin K. Li X. Yuan X. Xu P. Ni P. Xu D. Redefining tumor-associated macrophage subpopulations and functions in the tumor microenvironment. Front. Immunol. 2020 11 1731 10.3389/fimmu.2020.01731 32849616
    [Google Scholar]
  111. Yang Y. Andersson P. Hosaka K. Zhang Y. Cao R. Iwamoto H. Yang X. Nakamura M. Wang J. Zhuang R. Morikawa H. Xue Y. Braun H. Beyaert R. Samani N. Nakae S. Hams E. Dissing S. Fallon P.G. Langer R. Cao Y. The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages. Nat. Commun. 2016 7 1 11385 10.1038/ncomms11385 27150562
    [Google Scholar]
  112. Motegi S. Leitner W.W. Lu M. Tada Y. Sárdy M. Wu C. Chavakis T. Udey M.C. Pericyte-derived MFG-E8 regulates pathologic angiogenesis. Arterioscler. Thromb. Vasc. Biol. 2011 31 9 2024 2034 10.1161/ATVBAHA.111.232587 21737783
    [Google Scholar]
  113. Yamada K. Uchiyama A. Uehara A. Perera B. Ogino S. Yokoyama Y. Takeuchi Y. Udey M.C. Ishikawa O. Motegi S. MFG-E8 drives melanoma growth by stimulating mesenchymal stromal cell–induced angiogenesis and M2 polarization of tumor-associated macrophages. Cancer Res. 2016 76 14 4283 4292 10.1158/0008‑5472.CAN‑15‑2812 27197197
    [Google Scholar]
  114. Wu Z. Thierry K. Bachy S. Zhang X. Gamradt P. Hernandez-Vargas H. Mikaelian I. Tonon L. Pommier R. Zhao Y. Bertolino P. Hennino A. Pericyte stem cells induce Ly6G + cell accumulation and immunotherapy resistance in pancreatic cancer. EMBO Rep. 2023 24 4 e56524 10.15252/embr.202256524 36802267
    [Google Scholar]
  115. Zhu C. Chrifi I. Mustafa D. van der Weiden M. Leenen P.J.M. Duncker D.J. Kros J.M. Cheng C. CECR1-mediated cross talk between macrophages and vascular mural cells promotes neovascularization in malignant glioma. Oncogene 2017 36 38 5356 5368 10.1038/onc.2017.145 28534507
    [Google Scholar]
  116. Bose A. Barik S. Banerjee S. Ghosh T. Mallick A. Bhattacharyya Majumdar S. Goswami K.K. Bhuniya A. Banerjee S. Baral R. Storkus W.J. Dasgupta P.S. Majumdar S. Tumor-derived vascular pericytes anergize Th cells. J. Immunol. 2013 191 2 971 981 10.4049/jimmunol.1300280 23785117
    [Google Scholar]
  117. Ochs K. Sahm F. Opitz C.A. Lanz T.V. Oezen I. Couraud P.O. von Deimling A. Wick W. Platten M. Immature mesenchymal stem cell-like pericytes as mediators of immunosuppression in human malignant glioma. J. Neuroimmunol. 2013 265 1-2 106 116 10.1016/j.jneuroim.2013.09.011 24090655
    [Google Scholar]
  118. Valdor R. García-Bernal D. Riquelme D. Martinez C.M. Moraleda J.M. Cuervo A.M. Macian F. Martinez S. Glioblastoma ablates pericytes antitumor immune function through aberrant up-regulation of chaperone-mediated autophagy. Proc. Natl. Acad. Sci. USA 2019 116 41 20655 20665 10.1073/pnas.1903542116 31548426
    [Google Scholar]
  119. Galassi C. Chan T.A. Vitale I. Galluzzi L. The hallmarks of cancer immune evasion. Cancer Cell 2024 42 11 1825 1863 10.1016/j.ccell.2024.09.010 39393356
    [Google Scholar]
  120. Ruan J. Luo M. Wang C. Fan L. Yang S.N. Cardenas M. Geng H. Leonard J.P. Melnick A. Cerchietti L. Hajjar K.A. Imatinib disrupts lymphoma angiogenesis by targeting vascular pericytes. Blood 2013 121 26 5192 5202 10.1182/blood‑2013‑03‑490763 23632889
    [Google Scholar]
  121. Thijssen V.L.J.L. Paulis Y.W.J. Nowak-Sliwinska P. Deumelandt K.L. Hosaka K. Soetekouw P.M.M.B. Cimpean A.M. Raica M. Pauwels P. van den Oord J.J. Tjan-Heijnen V.C.G. Hendrix M.J. Heldin C.H. Cao Y. Griffioen A.W. Targeting PDGF‐mediated recruitment of pericytes blocks vascular mimicry and tumor growth. J. Pathol. 2018 246 4 447 458 10.1002/path.5152 30101525
    [Google Scholar]
  122. Cooke V.G. LeBleu V.S. Keskin D. Khan Z. O’Connell J.T. Teng Y. Duncan M.B. Xie L. Maeda G. Vong S. Sugimoto H. Rocha R.M. Damascena A. Brentani R.R. Kalluri R. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 2012 21 1 66 81 10.1016/j.ccr.2011.11.024 22264789
    [Google Scholar]
  123. Keskin D. Kim J. Cooke V.G. Wu C.C. Sugimoto H. Gu C. De Palma M. Kalluri R. LeBleu V.S. Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2. Cell Rep. 2015 10 7 1066 1081 10.1016/j.celrep.2015.01.035 25704811
    [Google Scholar]
  124. Han B. Li K. Wang Q. Zhang L. Shi J. Wang Z. Cheng Y. He J. Shi Y. Zhao Y. Yu H. Zhao Y. Chen W. Luo Y. Wu L. Wang X. Pirker R. Nan K. Jin F. Dong J. Li B. Sun Y. Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non–small cell lung cancer. JAMA Oncol. 2018 4 11 1569 1575 10.1001/jamaoncol.2018.3039 30098152
    [Google Scholar]
  125. Kang Y.K. Ryu M.H. Yoo C. Ryoo B.Y. Kim H.J. Lee J.J. Nam B.H. Ramaiya N. Jagannathan J. Demetri G.D. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): A randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 14 12 1175 1182 10.1016/S1470‑2045(13)70453‑4 24140183
    [Google Scholar]
  126. Schlumberger M. Tahara M. Wirth L.J. Robinson B. Brose M.S. Elisei R. Habra M.A. Newbold K. Shah M.H. Hoff A.O. Gianoukakis A.G. Kiyota N. Taylor M.H. Kim S.B. Krzyzanowska M.K. Dutcus C.E. de las Heras B. Zhu J. Sherman S.I. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl. J. Med. 2015 372 7 621 630 10.1056/NEJMoa1406470 25671254
    [Google Scholar]
  127. Sternberg C.N. Davis I.D. Mardiak J. Szczylik C. Lee E. Wagstaff J. Barrios C.H. Salman P. Gladkov O.A. Kavina A. Zarbá J.J. Chen M. McCann L. Pandite L. Roychowdhury D.F. Hawkins R.E. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J. Clin. Oncol. 2010 28 6 1061 1068 10.1200/JCO.2009.23.9764 20100962
    [Google Scholar]
  128. Grothey A. Cutsem E.V. Sobrero A. Siena S. Falcone A. Ychou M. Humblet Y. Bouché O. Mineur L. Barone C. Adenis A. Tabernero J. Yoshino T. Lenz H.J. Goldberg R.M. Sargent D.J. Cihon F. Cupit L. Wagner A. Laurent D. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013 381 9863 303 312 10.1016/S0140‑6736(12)61900‑X 23177514
    [Google Scholar]
  129. Llovet J.M. Ricci S. Mazzaferro V. Hilgard P. Gane E. Blanc J.F. de Oliveira A.C. Santoro A. Raoul J.L. Forner A. Schwartz M. Porta C. Zeuzem S. Bolondi L. Greten T.F. Galle P.R. Seitz J.F. Borbath I. Häussinger D. Giannaris T. Shan M. Moscovici M. Voliotis D. Bruix J. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008 359 4 378 390 10.1056/NEJMoa0708857 18650514
    [Google Scholar]
  130. Brose M.S. Nutting C.M. Jarzab B. Elisei R. Siena S. Bastholt L. de la Fouchardiere C. Pacini F. Paschke R. Shong Y.K. Sherman S.I. Smit J.W.A. Chung J. Kappeler C. Peña C. Molnár I. Schlumberger M.J. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: A randomised, double-blind, phase 3 trial. Lancet 2014 384 9940 319 328 10.1016/S0140‑6736(14)60421‑9 24768112
    [Google Scholar]
  131. Ravaud A. Motzer R.J. Pandha H.S. George D.J. Pantuck A.J. Patel A. Chang Y.H. Escudier B. Donskov F. Magheli A. Carteni G. Laguerre B. Tomczak P. Breza J. Gerletti P. Lechuga M. Lin X. Martini J.F. Ramaswamy K. Casey M. Staehler M. Patard J.J. Adjuvant sunitinib in high-risk renal-cell carcinoma after Nephrectomy. N. Engl. J. Med. 2016 375 23 2246 2254 10.1056/NEJMoa1611406 27718781
    [Google Scholar]
  132. Haas N.B. Manola J. Uzzo R.G. Flaherty K.T. Wood C.G. Kane C. Jewett M. Dutcher J.P. Atkins M.B. Pins M. Wilding G. Cella D. Wagner L. Matin S. Kuzel T.M. Sexton W.J. Wong Y.N. Choueiri T.K. Pili R. Puzanov I. Kohli M. Stadler W. Carducci M. Coomes R. DiPaola R.S. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): A double-blind, placebo-controlled, randomised, phase 3 trial. Lancet 2016 387 10032 2008 2016 10.1016/S0140‑6736(16)00559‑6 26969090
    [Google Scholar]
  133. Wu Y. Ma W. Liu W. Zhang S. Lactate: A pearl dropped in the ocean—an overlooked signal molecule in physiology and pathology. Cell Biol. Int. 2023 47 2 295 307 10.1002/cbin.11975 36511218
    [Google Scholar]
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