Maemura M, Akiyama S K, Woods V L, Dickson R B
Lombardi Cancer Research Center, Georgetown University, Washington, DC 20007, USA.
Clin Exp Metastasis. 1995 Jul;13(4):223-35. doi: 10.1007/BF00133478.
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.
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上α2β1整合素的表达及配体特异性。通过流式细胞术分析，我们发现α2β1整合素在这些细胞上普遍表达，但表达程度差异很大。未观察到其表达与其他已知细胞表型之间存在显著相关性。使用阻断抗体进行的底物附着试验表明，α2β1整合素是HMEC和几乎所有乳腺癌细胞上胶原蛋白的受体。然而，根据性类固醇受体状态以及上皮-间质转化标志物（即E-钙黏蛋白的缺失和波形蛋白的表达）评估，其对这些细胞层粘连蛋白结合的贡献似乎与细胞分化有关。两种不同的非恶性永生化HMEC群体（184A1N4和MCF-10A）包含能够将α2β1整合素用作层粘连蛋白受体的细胞。雌激素受体（ER）和E-钙黏蛋白呈阳性的乳腺癌细胞系（MCF-7、T47D、ZR75-1）也可将α2β1整合素用作层粘连蛋白受体。相反，α2β1整合素似乎无法与层粘连蛋白结合，或者在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）上是层粘连蛋白的非常次要的受体。这些发现表明，α2β1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控。α2β1整合素对细胞层粘连蛋白结合的贡献降低似乎与乳腺癌细胞恶性表型增加和上皮-间质转化有关。
