Radford K J, Thorne R F, Hersey P
Oncology and Immunology Unit, John Hunter Hospital, Newcastle, Australia.
J Immunol. 1997 Apr 1;158(7):3353-8.
CD63 belongs to the transmembrane 4 superfamily of membrane proteins and is expressed in several normal tissues as well as in melanoma cells. Previous reports have suggested that CD63 may play an important role in inhibiting melanoma progression, and this was supported by our studies showing that CD63 was associated with suppression of the growth of melanoma in nude mice. Recently, we and others have shown that CD63 may form noncovalent associations with beta1 integrins, which suggests that the function of CD63 may be related to that of integrins. To further explore the role of CD63 in melanoma, we transfected CD63 into a highly motile, CD63-negative melanoma cell line, KM3, which was shown to express alpha(v)beta5 as the predominant integrin with only trace amounts of beta1 integrins. Following transfection, CD63 was shown to associate with beta1 integrins, and beta1 expression appeared to be up-regulated. Cell motility in serum-containing media was markedly suppressed following transfection of CD63. This inhibition was potentiated by mAbs to CD63, and correlated with the level of CD63 expression. The CD63-transfected, but not the untransfected, melanoma cells showed increased adhesion and migration on the beta1 substrates, fibronectin, laminin, and collagen, whereas rates of migration were similar on the beta5 substrate, vitronectin. These results show that CD63 is involved in regulation of the motility of melanoma cells and their adhesion and migration on substrates associated with beta1 integrins. We suggest they provide further insights into the role of CD63 in tumor progression.
CD63属于膜蛋白的跨膜4超家族，在多种正常组织以及黑色素瘤细胞中均有表达。先前的报道表明，CD63可能在抑制黑色素瘤进展中发挥重要作用，我们的研究也支持了这一点，即CD63与裸鼠体内黑色素瘤生长的抑制相关。最近，我们和其他人发现CD63可能与β1整合素形成非共价结合，这表明CD63的功能可能与整合素有关。为了进一步探究CD63在黑色素瘤中的作用，我们将CD63转染到一种高迁移性、CD63阴性的黑色素瘤细胞系KM3中，该细胞系显示以α(v)β5作为主要整合素，仅含有微量的β1整合素。转染后，CD63显示与β1整合素结合，并且β1的表达似乎上调。转染CD63后，含血清培养基中的细胞迁移明显受到抑制。这种抑制作用被抗CD63单克隆抗体增强，并且与CD63的表达水平相关。转染了CD63的黑色素瘤细胞，而非未转染的细胞，在β1底物纤连蛋白、层粘连蛋白和胶原蛋白上的黏附和迁移增加，而在β5底物玻连蛋白上的迁移速率相似。这些结果表明，CD63参与调节黑色素瘤细胞的迁移以及它们在与β1整合素相关的底物上的黏附和迁移。我们认为这些结果为CD63在肿瘤进展中的作用提供了进一步的见解。
