CD44 variant isoform v10 is expressed on tumor-infiltrating lymphocytes and mediates hyaluronan-independent heterotypic cell-cell adhesion to melanoma cells.
CD44 is a family of cell-surface receptors on human lymphocytes that act as co-stimulatory molecules leading to the induction of effector functions in T cells. We have analyzed primary cutaneous malignant melanomas with clinical and histologic signs of tumor regression using immunohistochemistry and observed the predominant expression of the CD44 variant isoform v10 on CD3 CD4/CD8 co-expressing tumor-infiltrating lymphocytes (TIL). We further analyzed the role of CD44v10 in adhesion of lymphocytes to human melanoma cells. In contrast to CD44- lymphatic cells, CD44v10+ lymphatic cells strongly bound to cultured human melanoma cells and to frozen tissue samples of melanomas. Antibody blocking studies revealed a hyaluronan-, integrin-, and selectin-independent pathway of adhesion. Furthermore, CD44v10+ lymphatic cells exhibited significantly higher invasiveness in three-dimensional collagen matrices as compared with CD44H+ and CD44-negative lymphocytes. These results indicate that expression of CD44v10 on TIL may mediate adhesion to melanoma cells and result in gain of novel invasive properties.
Weimann
T K
TK
Department of Dermatology, School of Medicine, University of Essen, D-45122 Essen, Germany.
Wagner
C
C
Goos
M
M
Wagner
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SN
D002448:Cell Adhesion / Q000276:immunology; D045744:Cell Line, Tumor; D003094:Collagen; D014644:Genetic Variation; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D006820:Hyaluronic Acid / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009365:Neoplasm Regression, Spontaneous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D006820:Hyaluronic Acid; D003094:Collagen