Danen E H, van Muijen G N, van de Wiel-van Kemenade E, Jansen K F, Ruiter D J, Figdor C G
Department of Pathology, University Hospital, Nijmegen, The Netherlands.
Int J Cancer. 1993 May 8;54(2):315-21. doi: 10.1002/ijc.2910540225.
We compared integrin-mediated adhesion to extracellular matrix (ECM) components of cultured human melanocytes and 6 human melanoma cell lines with different metastatic capacities in nude mice. Cultured melanocytes and most melanoma cell lines adhered strongly to fibronectin (FN), whereas only highly metastatic cell lines adhered to laminin (LM), collagen type I (COI) and type IV (COIV). Adhesion to LM and CO could be blocked by anti-alpha 6 and anti-alpha 2 monoclonal antibodies (MAbs) respectively. This observation is consistent with the finding that expression of LM receptor alpha 6 beta 1 and LM/CO receptor alpha 2 beta 1 was low on melanocytes and non- or poorly metastatic cell lines, whereas these integrins were strongly expressed on highly metastatic cell lines. In addition, immunoprecipitation from [35S]-methionine-labeled cells demonstrated increased synthesis of alpha 6, alpha 2 and beta 1 in highly metastatic cell lines and immunohistochemistry showed expression of alpha 6 beta 1 and alpha 2 beta 1 only in xenograft lesions from highly metastatic cell lines. Furthermore, the observation that adhesion of melanocytes and non- or poorly metastatic cell lines could be stimulated with anti beta 1 MAbs demonstrates that these receptors, on these cells, are expressed in an inactive state. Our results suggest that alpha 2 beta 1 and alpha 6 beta 1 play a role in human melanoma metastasis in nude mice and demonstrate that interactions of these integrins with their ligands can be regulated at the level of surface expression and activation state of the receptor.
我们比较了培养的人黑素细胞以及6种在裸鼠中具有不同转移能力的人黑色素瘤细胞系通过整合素介导与细胞外基质（ECM）成分的黏附情况。培养的黑素细胞和大多数黑色素瘤细胞系都能强烈黏附于纤连蛋白（FN），而只有高转移细胞系能黏附于层粘连蛋白（LM）、Ⅰ型胶原（COI）和Ⅳ型胶原（COIV）。分别用抗α6和抗α2单克隆抗体（MAbs）可阻断对LM和CO的黏附。这一观察结果与以下发现一致：在黑素细胞和非转移或低转移细胞系上，LM受体α6β1和LM/CO受体α2β1的表达较低，而在高转移细胞系上这些整合素强烈表达。此外，从[35S]-甲硫氨酸标记的细胞进行免疫沉淀显示，高转移细胞系中α6、α2和β1的合成增加，免疫组织化学显示α6β1和α2β1仅在高转移细胞系的异种移植病变中表达。此外，用抗β1 MAbs可刺激黑素细胞和非转移或低转移细胞系的黏附这一观察结果表明，这些细胞上的这些受体以无活性状态表达。我们的结果表明，α2β1和α6β1在裸鼠中人黑色素瘤转移中起作用，并证明这些整合素与其配体的相互作用可在受体的表面表达和激活状态水平上受到调节。
