EXPRESSION AND STRUCTURAL FEATURES OF ENDOGLIN (CD105), A TRANSFORMING GROWTH-FACTOR-BETA-1 AND BETA-3 BINDING-PROTEIN, IN HUMAN-MELANOMA

Human endoglin (CD105) is a member of the transforming growth factor b eta (TGF-beta) receptor family that binds TGF-beta 1 and -beta 3, but not TGF-beta 2, on human endothelial cells. Immunohistochemical analys es demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAENDS, stained 50, 2 5 and 34% of intradermal naevi, primary and metastatic melanomas inves tigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysi s revealed that CD105 expressed by melanoma cells consists of a homodi meric protein with an apparent molecular weight of 180 and 95 kDa unde r non-reducing and reducing conditions. Cross-linking of I-125-labelle d TGF-beta 1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DS S) demonstrated that CD105 expressed on pigmented cells binds TGF-beta 1; the pattern of binding of TGF-beta 1 to melanoma cells was found t o be similar to that of human umbilical vein endothelial cells. The ad dition of exogenous, bioactive TGF-beta 1 significantly (P<0.05) inhib ited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altoge ther, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma ce lls by regulating their sensitivity to TGF-beta s.