Moseley Gregory W, Elliott Jill, Wright Mark D, Partridge Lynda J, Monk Peter N
Austin Research Institute, Kronheimer Building, A&RMC, Studley Road, Heidelberg, Victoria 3084, Australia.
Int J Cancer. 2003 Jul 10;105(5):613-6. doi: 10.1002/ijc.11144.
CD63 is a member of the tetraspanin superfamily of membrane glycoproteins that has been hypothesised to provide a structural network in the organisation of large multimolecular microdomains at cell membranes. Detailed analyses of the role of CD63 in these complexes through mutagenic studies have been limited, however, by the ubiquitous cellular expression of CD63 in vivo and in vitro. In an attempt to define CD63-null cell lines, we have analysed the expression of CD63 and other tetraspanins on a panel of human cancer cell lines. Similar expression patterns were seen between cell lines from melanomas, breast cancers and prostate cancers. The melanoma cell line KM3, however, described previously as a CD63-null human cell line, was found to express none of the 7 human tetraspanins tested. KM3 was identified definitively as a rat cell line by analysis of karyotype and antigen expression. Notably, KM3 was found to express the rat homologue of CD63. Conclusions concerning the function of human CD63 drawn from studies using KM3 cells therefore require re-evaluation as does the frequently cited hypothesis that CD63 expression is linked to melanoma progression. As KM3 is the only cell line thus far identified as CD63 negative, these results highlight the necessity for the production of a CD63 null system.
CD63是膜糖蛋白四跨膜超家族的成员，据推测它在细胞膜上大的多分子微区组织中提供结构网络。然而，通过诱变研究对CD63在这些复合物中的作用进行的详细分析受到了限制，因为CD63在体内和体外细胞中普遍表达。为了确定CD63缺失的细胞系，我们分析了一组人类癌细胞系中CD63和其他四跨膜蛋白的表达。黑色素瘤、乳腺癌和前列腺癌的细胞系之间观察到相似的表达模式。然而，先前被描述为CD63缺失的人类细胞系的黑色素瘤细胞系KM3，被发现在所测试的7种人类四跨膜蛋白中均不表达。通过核型分析和抗原表达分析，KM3被明确鉴定为大鼠细胞系。值得注意的是，KM3被发现表达CD63的大鼠同源物。因此，使用KM3细胞的研究得出的关于人类CD63功能的结论需要重新评估，同样，经常被引用的CD63表达与黑色素瘤进展相关的假设也需要重新评估。由于KM3是迄今为止唯一被鉴定为CD63阴性的细胞系，这些结果凸显了构建CD63缺失系统的必要性。
