Co-culture of human breast adenocarcinoma MCF-7 cells and human dermal fibroblasts enhances the production of matrix metalloproteinases 1, 2 and 3 in fibroblasts.
Co-culture of human breast adenocarcinoma MCF-7 cells and human dermal fibroblasts enhances the production of matrix metalloproteinases 1, 2 and 3 in fibroblasts.
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DOI：
10.1038/bjc.1995.200
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发表时间：
1995-05
影响因子：
8.8
通讯作者：
Mori, Y
中科院分区：
文献类型：
--
作者：
Ito, A;Nakajima, S;Sasaguri, Y;Nagase, H;Mori, Y
培养的人乳腺癌细胞系MCF-7和BT-20没有产生可测量量的基质金属蛋白酶（MMPs）。当MCF-7细胞与人真皮成纤维细胞共培养时，观察到MMP-1（间质胶原酶）、MMP-2（明胶酶A）、MMP-3（基质溶解素1）和金属蛋白酶组织抑制剂1（TIMP-1）的前体的产生增加。免疫组化研究表明，这些pro-MMPs主要来源于成纤维细胞，表明MCF-7细胞具有刺激基质细胞产生至少三种pro-MMPs和TIMP-1的作用。BT-20细胞也增加了皮肤成纤维细胞中pro-MMP-2和TIMP-1的产生，但不增加pro-MMP-1和pro-MMP-3的产生。正常乳腺上皮细胞仅促进TIMP-1的产生。为了进一步研究来自MCF-7细胞的刺激因子，制备并检查条件培养基和细胞膜。细胞膜组分增强pro-MMP-1和-3和TIMP-1的产生，但不增强pro-MMP-2的产生。另一方面，条件培养基增加了成纤维细胞中所有四种蛋白质的产生。这些观察结果表明，培养的乳腺癌MCF-7细胞产生可溶性和膜结合因子，这些因子刺激邻近基质细胞中pro-MMPs和TIMP-1的产生，但释放到培养基中的因子和与细胞膜相关的因子可能不同。正常和恶性细胞类型之间的这种通信可以部分地帮助癌细胞侵入和转移。
No measurable amounts of matrix metalloproteinases (MMPs) were produced by human breast adenocarcinoma cell lines MCF-7 and BT-20 in culture. When MCF-7 cells were co-cultured with human dermal fibroblasts enhanced production of precursors of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) was observed. Immunohistochemical studies indicated that these pro-MMPs originated primarily from the fibroblasts, suggesting that MCF-7 cells have a stimulatory effect on stromal cells to produce at least three pro-MMPs and TIMP-1. BT-20 cells also enhanced the production of pro-MMP-2 and TIMP-1 in the dermal fibroblasts, but not of pro-MMP-1 and pro-MMP-3. Normal mammary epithelial cells promoted only TIMP-1 production. To investigate further the stimulatory factors from MCF-7 cells, the conditioned medium and the cell membrane were prepared and examined. The cell membrane fraction enhanced the production of pro-MMP-1 and -3 and TIMP-1, but not of pro-MMP-2. The conditioned medium, on the other hand, augmented the production of all four proteins in the fibroblasts. These observations suggest that breast adenocarcinoma MCF-7 cells in culture produce both soluble and membrane-bound factor(s) which stimulate the production of pro-MMPs and TIMP-1 in neighbouring stromal cells, but the factor(s) released into the medium and that associated with cell membranes are probably different. Such communication between the normal and malignant cell types may, in part, assist the cancer cells to invade and metastasise.