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image of wM2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway
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Abstract

Background and objective

High morbidity, high mortality and poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the urgent need for novel therapeutic strategies against ESCC. The current study addresses the precise role of M2-like macrophages-derived CCL17 in ESCC progression and to thoroughly elucidate the intrinsic molecular mechanisms.

Methods

In this work, for functional experiments, Eca109 cells cultivated in M2-CM were treated with anti-IgG (50 µg/ml) or anti-CCL17 (50 µg/ml) to expound the tumor-promoting effects of M2-like macrophage-derived CCL17 in ESCC. Moreover, for rescue experiments, Eca109 cells were treated with CCL17 (50 ng/ml) and/or CCR4 antagonist AZD2098 (20 µM) to probe whether CCL17 could influence the malignant behaviors including migration, invasion and stemness of ESCC cells activating CCR4/ERK/PD-L1 pathway.

Results

Markedly enhanced CCL17 secretion was observed in M2-like macrophages. CCL17 bound to CCR4 to activate ERK/PD-L1 signaling. M2-like macrophages-derived CCL17 facilitated ESCC cell migration and invasion and enhanced stemness characteristics of ESCC cells, which were partially reserved by AZD2098 treatment. The tumor-promoting effects of M2-like macrophages-derived CCL17 on ECSS was depended on the activation of CCR4/ERK/PD-L1 pathway.

Conclusion

To conclude, M2-like macrophages-derived CCL17 could facilitate ESCC cell migration and invasion and enhance stemness characteristics of ESCC cells activating CCR4/ERK/PD-L1 signaling.

© 2024 Bentham Science Publishers
© 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2024-10-25
2024-11-26

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/content/journals/cmm/10.2174/0115665240312877241010123403
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wM2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0115665240312877241010123403
/content/journals/cmm/10.2174/0115665240312877241010123403
/content/journals/cmm/10.2174/0115665240312877241010123403
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  • Article Type:     Research Article
Keywords: ESCC ; CCR4 ; TAMs ; ERK/PD-L1 pathway ; CCL17

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