Schmidt Dirk-Steffen, Klingbeil Pamela, Schnölzer Martina, Zöller Margot
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany.
Exp Cell Res. 2004 Jul 15;297(2):329-47. doi: 10.1016/j.yexcr.2004.02.023.
The metastasizing subline of the rat pancreatic adenocarcinoma BSp73 expresses a set of membrane molecules, the combination of which has not been detected on non-metastasizing tumor lines. Hence, it became of interest whether these molecules function independently or may associate and exert specialized functions as membrane complexes. Separation of CD44v4-v7 containing membrane complexes in mild detergent revealed an association with the alpha3 integrin, annexin I, EpCAM, and the tetraspanins D6.1A and CD9. EpCAM and the tetraspanins associate selectively with CD44 variant (CD44v), but not with the CD44 standard (CD44s) isoform. The complexes are found in glycolipid-enriched membrane (GEM) microdomains, which are dissolved by stringent detergents, but the complexes are not destroyed by methyl-beta-cyclodextrin (MbetaCD) treatment, which implies that complex formation does not depend on a lipid-rich microenvironment. However, a complex-associated impact on cell-matrix and cell-cell adhesion as well as on resistance towards apoptosis essentially depended on the location in GEMs. Thus, CD44v-specific functions may well be brought about by complex formation of CD44v with EpCAM, the tetraspanins, and the alpha3 integrin. Because CD44v4-v7-EpCAM complex-specific functions strictly depended on the GEM localization, linker or signal-transducing molecules associating with the complex are likely located in GEMs.
大鼠胰腺腺癌BSp73的转移亚系表达一组膜分子，在非转移肿瘤系中未检测到这些分子的组合。因此，这些分子是独立发挥作用，还是可能结合并作为膜复合物发挥特殊功能，这一点变得很有趣。在温和去污剂中分离含CD44v4-v7的膜复合物，发现其与α3整合素、膜联蛋白I、上皮细胞黏附分子（EpCAM）以及四跨膜蛋白D6.1A和CD9相关联。EpCAM和四跨膜蛋白选择性地与CD44变异体（CD44v）结合，而不与CD44标准体（CD44s）亚型结合。这些复合物存在于富含糖脂的膜（GEM）微结构域中，该微结构域可被强去污剂溶解，但复合物不会因甲基-β-环糊精（MβCD）处理而被破坏，这意味着复合物的形成不依赖于富含脂质的微环境。然而，复合物对细胞-基质和细胞-细胞黏附以及对凋亡抗性的影响基本上取决于其在GEM中的位置。因此，CD44v的特异性功能很可能是由CD44v与EpCAM、四跨膜蛋白和α3整合素形成复合物所导致的。由于CD44v4-v7-EpCAM复合物的特异性功能严格依赖于GEM定位，与该复合物相关联的连接分子或信号转导分子可能位于GEM中。
