EXPRESSION AND LIGAND-BINDING OF ALPHA-2-BETA-1 INTEGRIN ON BREAST-CARCINOMA CELLS
EXPRESSION AND LIGAND-BINDING OF ALPHA-2-BETA-1 INTEGRIN ON BREAST-CARCINOMA CELLS
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DOI：
10.1007/bf00133478
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发表时间：
1995-07-01
影响因子：
4
通讯作者：
DICKSON, RB
中科院分区：
文献类型：
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作者：
MAEMURA, M;AKIYAMA, SK;DICKSON, RB
我们在体外检测了人乳腺上皮细胞（HMEC）和一组乳腺癌细胞系中α 2 β 1整合素的表达和配体特异性。我们发现α 2 β 1整合素在这些细胞上普遍表达，但通过流式细胞仪分析，其表达量相当低。它的表达与其他已知的细胞表型之间没有显著的相关性。使用封闭抗体的底物附着试验表明，α 2 β 1整合素作为HMEC和几乎所有乳腺癌细胞上胶原蛋白的受体。然而，其对这些细胞的层粘连蛋白结合的贡献似乎与细胞分化有关，如通过性类固醇受体状态和上皮-间充质转化的标志物（即E-钙粘蛋白的丢失和波形蛋白的表达）评估的。两种不同的非恶性永生化HMEC群体（184 A1 N4和MCF-10A）含有能够使用α 2 β 1整联蛋白作为层粘连蛋白受体的细胞。雌激素受体（ER）和E-钙粘蛋白阳性的乳腺癌细胞系（MCF-7、T47 D、ZR 75 -1）也可以使用α 2 β 1整联蛋白作为层粘连蛋白受体。相反，α 2 β 1整联蛋白似乎不能与层粘连蛋白结合，或者是表达波形蛋白的转移性ER阴性乳腺癌细胞（MDA-MB 231、MDA-MB 435和MDA-MB 436）上层粘连蛋白的非常小的受体。这些发现表明，α 2 β 1整合素的配体特异性，即其作为层粘连蛋白受体的功能，可能在乳腺癌细胞的恶性进展过程中受到调节。α 2 β 1整合素对细胞层粘连蛋白结合的贡献减少似乎与恶性表型增加和乳腺癌细胞的上皮-间质转化相关。
We examined the expression and ligand specificity of the alpha 2 beta 1 integrin on human mammary epithelial cells (HMEC) and a panel of breast carcinoma cell lines in vitro. We found that the alpha 2 beta 1 integrin was universally, but quite variably expressed on these cells by FACS analysis. No significant correlation was observed between its expression and other known cellular phenotypes. Substrate attachment assays using blocking antibodies demonstrated that alpha 2 beta 1 integrin served as a receptor for collagen on HMEC and almost all breast carcinoma cells. However, its contribution to laminin binding of these cells appeared to be related to cellular differentiation as evaluated by sex steroid receptor status and by markers of epithelial-mesenchymal transition, i.e. loss of E-cadherin and expression of vimentin. Two different populations of non-malignant immortalized HMEC (184A1N4 and MCF-10A) contained cells capable of using alpha 2 beta 1 integrin as a laminin receptor. Breast cancer cell lines positive for estrogen receptor (ER) and E-cadherin (MCF-7, T47D, ZR75-1) could also use alpha 2 beta 1 integrin as a laminin receptor. Conversely, alpha 2 beta 1 integrin appeared to be incapable of binding to laminin or to be a very minor receptor for laminin on metastatic ER-negative breast carcinoma cells that expressed vimentin (MDA-MB 231, MDA-MB 435, and MDA-MB 436). These findings suggest that the ligand specificity of alpha 2 beta 1 integrin, i.e. its function as a laminin receptor, may be regulated during the malignant progression of breast carcinoma cells. A reduced contribution of alpha 2 beta 1 integrin to the cellular laminin binding appears to be associated with an increased malignant phenotype and with an epithelial-mesenchymal transition of breast carcinoma cells.