Altomonte M, Montagner R, Fonsatti E, Colizzi F, Cattarossi I, Brasoveanu L I, Nicotra M R, Cattelan A, Natali P G, Maio M
Advanced Immunutherapy Unit, Centro di Riferimento Oncologico, Aviano, Italy.
Br J Cancer. 1996 Nov;74(10):1586-91. doi: 10.1038/bjc.1996.593.
Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas.
人内皮糖蛋白（CD105）是转化生长因子β（TGF-β）受体家族的成员，在人内皮细胞上能结合TGF-β1和TGF-β3，但不结合TGF-β2。免疫组织化学分析表明，CD105在黑素细胞系的正常细胞和肿瘤细胞上均有表达。抗CD105单克隆抗体MAEND3分别对所研究的皮内痣、原发性和转移性黑色素瘤的50%、25%和34%进行了染色，对12种黑色素瘤细胞系中的9种也进行了染色。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）分析显示，黑色素瘤细胞表达的CD105在非还原和还原条件下均由一种表观分子量为180 kDa和95 kDa的同二聚体蛋白组成。通过辛二酸二琥珀酰亚胺酯（DSS）将125I标记的TGF-β1与黑色素瘤细胞Mel 97交联，证明色素细胞上表达的CD105能结合TGF-β1；发现TGF-β1与黑色素瘤细胞的结合模式与人脐静脉内皮细胞相似。添加外源性生物活性TGF-β1能显著（P<0.05）抑制CD105阳性黑色素瘤细胞Mel 97的生长，但不影响CD105阴性黑色素瘤细胞F0-1的生长。这些数据总体表明，CD105在色素细胞上表达，可能通过调节人黑色素瘤细胞对TGF-β的敏感性，在其生物学过程中发挥功能相关作用。
