Kaufmann R, Frösch D, Westphal C, Weber L, Klein C E
Department of Dermatology, University of Ulm, Federal Republic of Germany.
J Cell Biol. 1989 Oct;109(4 Pt 1):1807-15. doi: 10.1083/jcb.109.4.1807.
The integrin VLA-3 is a cell surface receptor, which binds to fibronectin, laminin, collagen type I and VI (Takada, Y., E. A. Wayner, W. G. Carter, and M. E. Hemler. 1988. J. Cell. Biochem. 37:385-393) and is highly expressed in substrate adherent cultures of almost all human cell types. The ligand specificity of VLA-3 and the inhibition of cell adhesion by anti-VLA-3 monoclonal antibodies suggest its involvement in cell-substrate interaction. In normal tissues, VLA-3 is restricted to few cell types, notably the kidney glomeruli and basal cells of the epidermis. In the epidermis, VLA-3 is generally strongly expressed on the entire plasma membrane of basal cells and is not polarized towards the basement membrane (Klein, C. E., C. Cardon-Cardo, R. Soehnchen, R. J. Cote, H. F. Oettgen, M. Eisinger, and L. J. Old. 1987. J. Invest. Dermatol. 89:500-507). Based on this finding we speculated that, in addition to a role of VLA-3 for adhesion of cells to substrate, it could also be relevant for cell-cell interaction. To investigate this, we ultrastructurally localized VLA-3 on the surface of cultured cells by immunoelectron microscopy. In accordance with our concept, we found VLA-3 strongly associated with intercellular contact sites. Interestingly, very little immunoreactivity was detected at the under-surface of cells which had been cultured for 18-32 h. This observation was unexpected but is consistent with previous findings (Kantor, R. R. S., M. J. Mattes, K. D. Lloyd, L. J. Old, and A. P. Albino. 1987. J. Biol. Chem. 262:15158-15165) which suggest that the association of VLA-3 with the basal surface of substrate adherent tumor cells is a late event occurring after days of culture under confluent conditions. However, we cannot formally rule out VLA-3 expression at the undersurface of cells under our experimental conditions, since VLA-3 molecules at this location could be inaccessible for in situ labeling of unfixed cells because of spatial interferences. In conclusion, our results demonstrate the expression of VLA-3 at intercellular contact sites of cultured cells supporting the concept that it may be relevant for intercellular interactions also.
整合素VLA - 3是一种细胞表面受体，它可与纤连蛋白、层粘连蛋白、I型和VI型胶原结合（高田洋、E.A.韦纳、W.G.卡特和M.E.亨勒，1988年，《细胞生物化学杂志》37卷：385 - 393页），在几乎所有人类细胞类型的贴壁培养物中高表达。VLA - 3的配体特异性以及抗VLA - 3单克隆抗体对细胞黏附的抑制作用表明它参与细胞与底物的相互作用。在正常组织中，VLA - 3仅限于少数细胞类型，特别是肾小球和表皮基底细胞。在表皮中，VLA - 3通常在基底细胞的整个质膜上强烈表达，且不向基底膜极化（克莱因，C.E.、C.卡尔东 - 卡多、R.索恩琴、R.J.科特、H.F.奥滕根、M.艾辛格和L.J.奥尔德，1987年，《皮肤病学研究杂志》89卷：500 - 507页）。基于这一发现，我们推测，除了VLA - 3在细胞与底物黏附中的作用外，它可能也与细胞间相互作用有关。为了对此进行研究，我们通过免疫电子显微镜在超微结构水平上对培养细胞表面的VLA - 3进行定位。与我们的设想一致，我们发现VLA - 3与细胞间接触位点紧密相关。有趣的是，在培养18 - 32小时的细胞下表面检测到的免疫反应性非常低。这一观察结果出乎意料，但与先前的发现（坎托，R.R.S.、M.J.马特斯、K.D.劳埃德、L.J.奥尔德和A.P.阿尔比诺，1987年，《生物化学杂志》262卷：15158 - 15165页）一致，这些发现表明VLA - 3与贴壁肿瘤细胞基底表面的结合是在汇合条件下培养数天后发生的晚期事件。然而，我们不能完全排除在我们的实验条件下细胞下表面存在VLA - 3表达，因为由于空间干扰，该位置的VLA - 3分子可能无法用于未固定细胞的原位标记。总之，我们的结果证明了VLA - 3在培养细胞的细胞间接触位点表达，支持了它可能也与细胞间相互作用相关的观点。
