Jeffers M, Rao M S, Rulong S, Reddy J K, Subbarao V, Hudson E, Vande Woude G F, Resau J H
Advanced BioScience Laboratories, Inc.-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Cell Growth Differ. 1996 Dec;7(12):1805-13.
Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector for cells expressing the Met tyrosine kinase receptor. In this investigation, we show that pancreatic oval cells express Met and exhibit a proliferative response to HGF/SF. Additionally, we found that oval cells treated transiently with this factor become "scattered," whereas those exposed to HGF/ SF for extended periods of time form branching tubular structures. These structures possess true lumens, which are lined by cells with ductal features, including apical microvilli, well-developed intercellular junctions, interdigitation of plasma membranes, and abundant cytoplasmic organelles. Interestingly, these ductal structures are formed by HGF/SF-treated cells cultured on plastic dishes in the absence of exogenous extracellular matrix components. Consistent with their ability to form ductal structures in vitro, we found that pancreatic oval cells form ductal adenocarcinomas in nude mice. This study supports the involvement of HGF/SF-Met signaling in the growth, migration, and morphogenesis of pancreatic oval cells and may have important implications for the expansion and morphogenic differentiation of these cells during developmental, regenerative, and neoplastic growth.
肝细胞生长因子/分散因子（HGF/SF）是一种对表达Met酪氨酸激酶受体的细胞具有多效性作用的效应因子。在本研究中，我们发现胰腺卵圆细胞表达Met，并对HGF/SF表现出增殖反应。此外，我们发现用该因子短暂处理的卵圆细胞会“分散”，而长时间暴露于HGF/SF的细胞则形成分支管状结构。这些结构具有真正的管腔，其内壁由具有导管特征的细胞构成，包括顶端微绒毛、发育良好的细胞间连接、质膜的指状交叉以及丰富的细胞质细胞器。有趣的是，这些导管结构是由在无外源细胞外基质成分的塑料培养皿上培养的经HGF/SF处理的细胞形成的。与它们在体外形成导管结构的能力一致，我们发现胰腺卵圆细胞在裸鼠体内形成导管腺癌。本研究支持HGF/SF-Met信号通路参与胰腺卵圆细胞的生长、迁移和形态发生，并且可能对这些细胞在发育、再生和肿瘤生长过程中的扩增和形态发生分化具有重要意义。
