Differential Involvement of Myosin II and VI in the Spontaneous and SDF- 1-induced Migration of Adult CD133+ Hematopoietic Stem/Progenitor Cells and Leukemic Cells

Cell migration is an essential characteristic of life. However, the indispensable, physiological migration of embryonic and adult stem cells, leukocytes, and fibroblasts is opposed to the pathological migration of tumor cells during metastasis formation. Leukemic cells take a special position, since they combine characteristics of leukocyte and tumor cell migration. Although migration occurs in many variants with regard to dynamics and molecular mechanisms, myosin is generally needed to generate locomotory forces in all of the aformentioned cells. Our work aims to the understanding on the involvement of different myosin isotypes in the migration of leukocytes and leukemic cells at various stages of differentiation. By means of our three-dimensional, collagen-based migration assay, we investigated the involvement of nonmuscle myosin II and myosin VI in the migration of adult CD133+ hematopoietic stem/progenitor cells (HSPCs) as well as of four leukemic cell lines (Jurkat, Molt-4, NB-4, Dohh-2) and cells from leukemia patients. We show that the spontaneous, matrix-induced migration of CD133+ HSPCs solely depends on the activity of myosin VI, whereas the stromal cellderived factor (SDF)-1-induced migration requires both myosin isotypes. In contrast, leukemic cells engage both myosin isotypes for the spontaneous and the SDF-1-induced migration with varying proportions. Our previous studies have shown that the migration of differentiated leukocytes is exclusively based on non-muscle myosin II. We conclude that the proportionate involvement of non-muscle myosin II and myosin VI varies due to the differentiation state of the cells. The involvement of myosin VI decreases with the grade of differentiation, whereas the role of non-muscle myosin II increases.