Mammary fibroblasts regulate morphogenesis of normal and tumorigenic breast epithelial cells by mechanical and paracrine signals

乳腺成纤维细胞通过机械和旁分泌信号调节正常和致瘤乳腺上皮细胞的形态发生

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作者:Inke Lühr, Andreas Friedl, Thorsten Overath, Andreas Tholey, Thomas Kunze, Felix Hilpert, Susanne Sebens, Norbert Arnold, Frank Rösel, Hans-Heinrich Oberg, Nicolai Maass, Christoph Mundhenke, Walter Jonat, Maret Bauer

Abstract

Stromal factors play a critical role in the development of the mammary gland. Using a three dimensional-coculture model we demonstrate a significant role for stromal fibroblasts in the regulation of normal mammary epithelial morphogenesis and the control of tumor growth. Both soluble factors secreted by fibroblasts and fibroblast-derived modifications of the matrix compliance contribute to the regulation of epithelial cell morphogenesis. Readjustment of matrix tension by fibroblasts can even induce a phenotypic reversion of breast carcinoma cells. These data offer a basis to develop new strategies for the normalization of the tumor stroma as an innovative target in cancer therapy.

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