| Summary: | 碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 89 === CD44, a widely expressed cell surface glycoprotein, plays a major role in cell-cell adhesion, cell-substrate interaction, lymphocyte homing and tumor metastasis. For tumor metastasis through blood vessel and lymphatic vessel pathway, tumor cells must first adhere to the endothelial cells. Recent studies have indicated that highly expressed CD44 in certain types of tumors is associated with hematogenic spread of cancer cells. However, the functional relevance of CD44 on tumor cells to metastasis remains unknown. In this study, we investigated the mechanisms of adhesion and transendothelial migration of tumor cells using breast cancer cell lines. The results showed that breast cancer cells expression high levels of CD44. We demonstrated that CD44 cross-linking markedly induces the expression of lymphocyte function-associated antigen 1(LFA-1) and very late antigen 4 (VLA-4) by using flow cytometric analysis, immunofluorescence staining and western blot. CD44 cross-linking also caused subsequently LFA-1 and VLA-4-mediated cell adhesion to enodthelial cells. Furthermore, CD44 cross-linking-induced LFA-1 and VLA-4 expression facilitate transendothelial cancer cell migration, Both LFA-1 and VLA-4-mediated adhesion and transendothelial cancer cell migration can be abolished by anti-LFA-1 and anti-VLA-4 antibodies. These data demonstrate that CD44 cross-linking induced LFA-1 and VLA-4 expression in human breast cancer cells amplified the integrin-mediated adhesion to the endothelial cells, which subsequently results in the transendothelial migration of breast cancer cells.
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