Restricted expression of membrane type 1-matrix metalloproteinase by myofibroblasts adjacent to human breast cancer cells
Restricted expression of membrane type 1-matrix metalloproteinase by myofibroblasts adjacent to human breast cancer cells
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DOI：
10.1002/ijc.11012
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发表时间：
2003-05-20
影响因子：
6.4
通讯作者：
Noel, A
中科院分区：
文献类型：
--
作者：
Bisson, C;Blacher, S;Noel, A
膜型基质金属蛋白酶-1(MT1-MMPs)最初发现于乳腺癌，具有激活其他MMPs(MMP2和MMP13)和降解细胞外基质的能力。本研究旨在定位和鉴定MT1-基质金属蛋白酶在乳腺癌中的表达细胞。免疫组织化学和原位杂交图像的纹理分析准确地显示了肌成纤维细胞中α-平滑肌肌动蛋白(α-SM-肌动蛋白)和MT1-基质金属蛋白酶的共同表达。MT1-MMPs的表达仅限于与肿瘤细胞密切接触的肌成纤维细胞。与之形成鲜明对比的是，在靠近和远离癌细胞簇的ASM肌动蛋白阳性和阴性细胞中，基质金属蛋白酶-2的表达更为广泛。与正常乳腺成纤维细胞相比，我们的体外观察结果与乳腺肿瘤αSM肌动蛋白阳性成纤维细胞中MT1-MMP1的高表达和MMP2的激活是一致的。总之，这些结果表明肌成纤维细胞是乳腺癌中MT1-基质金属蛋白酶的主要产生细胞，并强调了基质-上皮细胞相互作用在乳腺癌进展中的重要性。(C)2003年Wiley-Liss，Inc.
The membrane type-1 matrix metalloproteinase (MT1-MMP), a protease originally identified in breast carcinoma, is characterized by its capacity to Activate other MMPs (MMP-2 and MMP-13) and to degrade extracellular matrix. Our study was undertaken to localize and identify the MT1-MMP expressing cells in human breast adenocarcinomas. A textural analysis of images obtained by immunohistochemistry and in situ hybridization showed precisely the co-expression of alpha smooth muscle actin (alphaSM actin) and MT1-MMP in myofibroblasts. MT1-MMP expression is confined to myofibroblasts in close contact with tumor cells. In sharp contrast, the expression of MMP-2 was more widely distributed in both aSM actin positive and negative cells close to and at distance from cancer cell clusters. Our in vitro observations are consistent with the higher level of MT1-MMP expression and of MMP-2 activation observed in alphaSM actin positive fibroblasts derived from breast tumors, at compared to normal breast fibroblasts. Collectively, these results implicate myofibroblasts as major producer of MT1-MMP in breast cancer and emphasize the importance of stromal-epithelial cell interactions in their progression. (C) 2003 Wiley-Liss, Inc.