Silberstein G B, Strickland P, Coleman S, Daniel C W
Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz 95064.
J Cell Biol. 1990 Jun;110(6):2209-19. doi: 10.1083/jcb.110.6.2209.
Exogenous transforming growth factor beta (TGF-beta 1) was shown in earlier studies to reversibly inhibit mouse mammary ductal growth. Using small plastic implants to treat regions of developing mammary glands in situ, we now report that TGF-beta 1 growth inhibition is associated with an ectopic accumulation of type I collagen messenger RNA and protein, as well as the glycosaminoglycan, chondroitin sulfate. Both macromolecules are normal components of the ductal extracellular matrix, which, under the influence of exogenous TGF-beta 1, became unusually concentrated immediately adjacent to the epithelial cells at the tip of the ductal growth points, the end buds. Stimulation of extracellular matrix was confined to aggregations of connective tissue cells around affected end buds and was not present around the TGF-beta 1 implants themselves, indicating that the matrix effect was epithelium dependent. Ectopic matrix synthesis was specific for TGF-beta 1 insofar as it was absent at ducts treated with other growth inhibitors, or at ducts undergoing normal involution in response to endogenous regulatory processes. These findings are consistent with the matrix-stimulating properties of TGF-beta 1 reported for other systems, but differ in their strict dependence upon epithelium. A possible role for endogenous TGF-beta 1 in modulating a mammary epithelium-stroma interaction is suggested.
早期研究表明，外源性转化生长因子β（TGF-β1）可可逆性抑制小鼠乳腺导管生长。我们利用小型塑料植入物对发育中的乳腺区域进行原位处理，现报告TGF-β1的生长抑制作用与I型胶原信使核糖核酸及蛋白质以及糖胺聚糖硫酸软骨素的异位积聚有关。这两种大分子都是导管细胞外基质的正常成分，在外源性TGF-β1的影响下，它们在导管生长点（即终末芽）顶端的上皮细胞紧邻处异常浓缩。细胞外基质的刺激仅限于受影响终末芽周围的结缔组织细胞聚集处，而在TGF-β1植入物本身周围则不存在，这表明基质效应依赖于上皮细胞。异位基质合成对TGF-β1具有特异性，因为在用其他生长抑制剂处理的导管或因内源性调节过程而正常退化的导管中不存在这种情况。这些发现与报道的TGF-β1在其他系统中的基质刺激特性一致，但在对上皮细胞的严格依赖性方面有所不同。这提示内源性TGF-β1在调节乳腺上皮-基质相互作用中可能发挥作用。
