Heregulin and retinoids synergistically induce branching morphogenesis of breast cancer cells cultivated in 3D collagen gels
Heregulin and retinoids synergistically induce branching morphogenesis of breast cancer cells cultivated in 3D collagen gels
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DOI：
10.1002/jcp.10237
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发表时间：
2003-05-01
影响因子：
5.6
通讯作者：
Grunt, TW
中科院分区：
文献类型：
--
作者：
Offterdinger, M;Schneider, SM;Grunt, TW
C-erbB和类维生素A受体信号传导控制乳腺上皮细胞增殖、分化和形态。在这里，我们研究了c-erbB特异性配体，如heregulin和类维生素A对非恶性（原发性，MTSV 1 -7）和恶性（T47 D，SKBR-3）人乳腺上皮细胞（HMEC）在三维胶原蛋白I型凝胶培养的形态发生活性。这些细胞对c-erbB和类维生素A受体均呈阳性。非恶性原发性HMEC自发地在胶原中形成分支结构，而SV 40大T抗原永生化的非致瘤性MTSV 1 -7自发地形成球，并需要调蛋白或类维生素A X受体α选择性类维生素A Ro 25-7386用于分支，这通过两种类型的试剂的组合进一步刺激。在恶性细胞中，heregulin单独诱导球形成，并与Ro 25-7386（T47 D）或视黄酸受体α选择性AM 580（SKBR-3）合作进行分支形态发生，这伴随着α（2）β（1）-整联蛋白和E-钙粘蛋白亚细胞分布的变化，以及c-erbB-2、-3或-4的下调。调蛋白和/或类维生素A相应地增加了恶性细胞与I型胶原的整合素依赖性粘附。我们的数据表明c-erbB和维甲酸受体途径在形态发生和免疫表型分化水平的合作信号。J.细胞。195：260-275，2003. (C)2003 Wiley-Liss，Inc.
C-erbB and retinoid receptor signaling control mammary epithelial cell proliferation, differentiation, and morphology. Here, we examined the morphogenetic activities of c-erbB specific ligands such as heregulin and of retinoids on nonmalignant (primary, MTSV1-7) and malignant (T47D, SKBR-3) human mammary epithelial cells (HMEC) cultivated in 3D collagen type I gels. These cells are positive for both c-erbB and retinoid receptors. Non-malignant primary HMEC spontaneously formed branched structures in collagen, whereas SV40 large T antigen-immortalized non-tumorigenic MTSV1-7 spontaneously formed balls and required heregulin or retinoid X receptor alpha-selective retinoid Ro 25-7386 for branching, which was further stimulated by combination of both types of agents. In malignant cells, heregulin alone induced ball formation and cooperated either with Ro 25-7386 (T47D) or with retinoic acid receptor alpha-selective AM580 (SKBR-3) for branching morphogenesis, which was accompanied by changes in the subcellular distribution Of alpha(2)beta(1)-integrin and E-cadherin, and by down-regulation of c-erbB-2, -3, or -4. Heregulin and/or retinoids correspondingly increased the integrin-dependent adhesion of malignant cells to type I collagen. Our data demonstrate cooperative signaling of c-erbB and retinoid receptor pathways at the levels of morphogenesis and immunophenotypic differentiation. J. Cell. Physiol. 195: 260-275, 2003. (C) 2003 Wiley-Liss, Inc.