CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation

被引:151
作者
Ahrens, T
Assmann, V
Fieber, C
Termeer, CC
Herrlich, P
Hofmann, M
Simon, JC
机构
[1] Univ Freiburg, Dept Dermatol, D-79104 Freiburg, Germany
[2] St Thomas Hosp, Richard Dimbleby Dept Canc Res, London, England
[3] Forschungszentrum Karlsruhe, Inst Genet, D-76021 Karlsruhe, Germany
[4] LION Biosci AG, Heidelberg, Germany
关键词
CD44; hyaluronic acid; IHABP melanoma;
D O I
10.1046/j.1523-1747.2001.00236.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Interactions of the extracellular matrix component hyaluronic acid and its cellular receptors CD44 and RHAMM/IHABP have been linked to tumor progression and metastasis formation. We investigated the expression and hyaluronic-acid-dependent functions of CD44 and RHAMM/IHABP in human melanoma. Immunohistochemistry of tumor specimens at different stages of melanoma progression revealed an increased expression of CD44 and RHAMM/IHABP, High mRNA expression of CD44 was found in three highly tumorigenic melanoma cell lines compared with less tumorigenic melanoma cells or nontransformed melanocytes. RHAMM/IHABP expression was upregulated in all cell lines analyzed but not in melanocytes. In contrast to the cell surface localization of CD44, RHAMM/IHABP was detected exclusively within the cytoplasm of melanoma cells. Binding and adhesion of melanoma cells to hyaluronic acid is mainly CD44 dependent as it was inhibited to 60%-80% by an anti-CD44 monoclonal antibody whereas anti-RHAMM/IHABP sera had no effect, Culture of melanoma cells in the presence of hyaluronic acid resulted in a dose-dependent, CD44-mediated increase of melanoma cell proliferation and enhanced release of basic fibroblast growth factor and transforming growth factor pi. We conclude that (i) the expression of CD44 and RHAMM/IHABP is increased during melanoma progression, (ii) CD44 is the principal hyaluronic acid surface receptor on melanoma cells, and (iii) the hyaluronic-acid-induced increase of the proliferative capacity of melanoma cells is mainly dependent on CD44-hyaluronic acid interactions.
引用
收藏
页码:93 / 101
页数:9
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