人卵巢上皮癌的转移传播是由α - β -整合素介导的与I型胶原的相互作用促进的。

D A Fishman, A Kearns, K Chilukuri, L M Bafetti, E A O'Toole, J Georgacopoulos, M J Ravosa, M S Stack
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引用次数: 75

摘要

上皮性卵巢癌的转移传播被认为是通过肿瘤细胞脱落进入腹腔,随后粘附并侵入覆盖在腹腔内容物上的间皮。在这项研究中,我们利用短期原代培养来分析特异性细胞外基质蛋白对人类卵巢上皮癌细胞特性的影响,这些特性有助于侵袭性表型。细胞基质黏附谱分析表明卵巢癌细胞优先黏附于I型胶原。免疫沉淀分析表明,胶原结合的α 2 β a1整合素存在于生物素标记的卵巢癌细胞膜中,针对α 2和β a1整合素亚基的阻断抗体抑制了细胞粘附。与对照肽Ala-Gly-Glu-Ala (AGEA)相比,α 2 β 1结合肽Asp-Gly-Glu-Ala (DGEA)在阻断胶原粘附方面也具有中等效果。蛋白包被胶体金盖板上的细胞运动分析表明,卵巢癌细胞优先在I型胶原包被表面迁移。I型胶原以浓度依赖性、可饱和的方式促进迁移,在胶原包被浓度为50微克/毫升时观察到最大迁移。针对alpha2和beta1整合素亚基的抗体和gea肽可抑制胶原上的迁移,这为alpha2beta1整合素在卵巢癌细胞运动中的作用提供了证据。在I型胶原凝胶上培养卵巢癌细胞导致基质金属蛋白酶2酶原转化为66-kD形式的显著增加,这表明与胶原的粘附也影响基质降解蛋白酶。这些数据表明,α 2 β -整合素介导的卵巢癌细胞与I型胶原蛋白的相互作用可能在多个层面上促进卵巢癌细胞的转移传播。I型胶原蛋白普遍存在于卵巢癌患者的间皮细胞外基质和腹腔中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.

Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the mesothelial extracellular matrix and in the peritoneal cavity of ovarian carcinoma patients, may function on multiple levels to promote metastatic dissemination of ovarian carcinoma cells.

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