Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration.
Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration.
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发表时间：
1990-08
期刊：
影响因子：
11.2
通讯作者：
K. Yamada;D. Kennedy;S. Yamada;H. Gralnick;Wen‐Tien Chen;S. K. Akiyama
中科院分区：
文献类型：
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作者：
K. Yamada;D. Kennedy;S. Yamada;H. Gralnick;Wen‐Tien Chen;S. K. Akiyama
人肿瘤细胞的迁移和侵袭过程可能涉及特异性细胞表面受体，例如细胞外基质分子纤连蛋白、层粘连蛋白和胶原蛋白的受体。我们已经研究了几个这些受体的作用，使用一组针对β 1整合素家族的单克隆抗体，以及一系列的合成肽报道抑制这些蛋白质与细胞表面的各种相互作用。发现肿瘤细胞迁移的最一般的抑制剂是抗β 1单克隆抗体13，当纤连蛋白是迁移底物时，其抑制人HT-1080纤维肉瘤细胞、5637膀胱癌细胞、VA 13病毒转化体和HCT 116结肠癌细胞的迁移。此外，该抗体在阻断细胞在层粘连蛋白上的迁移以及在三维胶原凝胶内的迁移方面特别有效。它还在低至1微克/毫升的浓度下在重构基底膜侵袭测定（Matrigel测定）中抑制体外侵袭。因此，β 1类整合素似乎在多种人类肿瘤细胞系的几种类型的迁移中发挥核心作用。抗α 5纤连蛋白受体单克隆抗体16也显着抑制迁移的纤连蛋白，但不是在其他基板上，在3的4个细胞系。相反，抗α 2单克隆抗体F17显著抑制迁移的3维胶原凝胶，但不是在其他基板上，牵连的α 2 β 1整合素系统中的迁移的肿瘤细胞在胶原基质。以前报道的一系列抑制正常细胞与纤连蛋白、层粘连蛋白和胶原蛋白相互作用的合成肽也被测试为肿瘤细胞迁移的抑制剂。含有Arg-Gly-Asp粘附识别信号的肽具有部分抑制作用，但偶尔例外，大多数其他肽对迁移没有影响。我们的研究结果表明，几个特定的β 1整合素在人类肿瘤细胞迁移的核心重要性，并显示单克隆抗体治疗在体外阻断这一过程的有效性。
The processes of migration and invasion by human tumor cells are likely to involve specific cell surface receptors, such as receptors for the extracellular matrix molecules fibronectin, laminin, and collagen. We have examined the roles of several of these receptors using a set of monoclonal antibodies directed against the beta 1 integrin family, as well as a series of synthetic peptides reported to inhibit various interactions of each of these proteins with the cell surface. The most general inhibitor of tumor cell migration was found to be the anti-beta 1 monoclonal antibody 13, which inhibited the migration of human HT-1080 fibrosarcoma cells, 5637 bladder carcinoma cells, VA13 viral transformants, and HCT 116 colon carcinoma cells when fibronectin was the migration substrate. Moreover, this antibody was particularly effective in blocking cell migration on laminin, as well as migration within 3-dimensional collagen gels. It also inhibited in vitro invasiveness in a reconstituted basement membrane invasion assay (Matrigel assay) at concentrations as low as 1 microgram/ml. Integrins of the beta 1 class thus appear to play a central role in several types of migration by a variety of human tumor cell lines. Anti-alpha 5 fibronectin receptor monoclonal antibody 16 also significantly inhibited migration on fibronectin, but not on other substrates, in 3 of the 4 cell lines. Conversely, anti-alpha 2 monoclonal antibody F17 strikingly inhibited migration in 3-dimensional collagen gels, but not on other substrates, implicating the alpha 2 beta 1 integrin system in migration of tumor cells within collagenous matrices. A series of synthetic peptides previously reported to inhibit interactions of normal cells with fibronectin, laminin, and collagen were also tested as inhibitors of tumor cell migration. Peptides containing the Arg-Gly-Asp adhesive recognition signal were partially inhibitory, but with occasional exceptions, most other peptides had no effects on migration. Our results indicate the central importance of several specific beta 1 integrins in human tumor cell migration and show the effectiveness of monoclonal antibody treatment in blocking this process in vitro.