Mammary fibroblast-derived hepatocyte growth factor and mammogenic hormones stimulate the growth of mouse mammary epithelial cells in primary culture
Mammary fibroblast-derived hepatocyte growth factor and mammogenic hormones stimulate the growth of mouse mammary epithelial cells in primary culture
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DOI：
10.1507/endocrj.46.359
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发表时间：
1999-06-01
影响因子：
2
通讯作者：
Enami, J
中科院分区：
文献类型：
--
作者：
Sasaki, M;Enami, J
最近，我们从小鼠乳腺成纤维细胞条件培养基中分离出一种乳腺生长因子，并将其鉴定为人HGF（肝细胞生长因子）的同源物（Sasaki等，Biochem Biophys Res Commun 199：772-779，1994）。为了阐明乳腺成纤维细胞来源的HGF在体内乳腺上皮细胞生长中的作用，我们在本研究中使用重组小鼠HGF并研究其对小鼠乳腺上皮细胞原代培养物生长的影响。HGF不仅在单层培养中，而且在三维胶原凝胶基质培养中刺激乳腺上皮细胞的生长。相反，乳房激素，即，催乳素和孕酮仅在细胞在胶原凝胶基质中培养时刺激乳腺上皮细胞的生长，这表明三维培养条件对于观察体内所见的致乳房激素的生长刺激作用是必要的。在这些三维培养条件下，还观察到HGF和促乳腺激素的累加效应。北方印迹分析显示，HGF mRNA在乳腺以及培养的乳腺成纤维细胞中表达，但在培养的乳腺上皮细胞中不表达，表明HGF优先由乳腺的基质成纤维细胞产生。因此，这些观察结果表明HGF作为乳腺基质成纤维细胞衍生的生长因子的作用，其与促乳腺激素合作，刺激体内乳腺上皮细胞的生长。
We recently isolated a mammary growth factor from mouse mammary fibroblast-conditioned medium and identified it as a homologue of human HGF (hepatocyte growth factor) (Sasaki et al. Biochem Biophys Res Commun 199: 772-779, 1994). To elucidate the role of mammary fibroblast-derived HGF in mammary epithelial cell growth in vivo, we used recombinant mouse HGF and examined its effect on the growth of primary cultures of mouse mammary epithelial cells in this study. HGF stimulated the growth of mammary epithelial cells not only in monolayer culture but also in three-dimensional collagen gel matrix culture. In contrast, mammogenic hormones, i.e., prolactin and progesterone, stimulated the growth of mammary epithelial cells only when the cells were cultured in a collagen gel matrix, suggesting that the three-dimensional culture conditions are necessary to observe the growth-stimulatory effect of mammogenic hormones seen in vivo. Under these three-dimensional culture conditions, an additive effect of HGF and mammogenic hormones was also seen. Northern blot analysis revealed that HGF mRNA was expressed in the mammary gland as well as in cultured mammary fibroblasts but not in cultured mammary epithelial cells, indicating that HGF is produced preferentially by the stromal fibroblasts of the mammary gland. These observations thus suggest a role for HGF as a mammary stromal fibroblast-derived growth factor which, in cooperation with mammogenic hormones, stimulates the growth of mammary epithelial cells in vivo.