Yashiro M, Chung Y S, Kubo T, Hato F, Sowa M
First Department of Surgery, Osaka City University Medical School, Japan.
Br J Cancer. 1996 Oct;74(7):1096-103. doi: 10.1038/bjc.1996.496.
Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer cells invade into the submucosa of the stomach. To investigate the mechanisms responsible for the rapid proliferation, the growth interaction between gastric cancer cells and fibroblasts was examined. Human gastric cancer cell lines established from scirrhous carcinoma or well-differentiated adenocarcinoma were used. Human fibroblast cell lines were obtained from various organs. The growth interaction between gastric cancer cells and fibroblasts was examined by calculating the number of cancer cells or by measuring [3H]thymidine incorporation of cancer cells. Gastric fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of well-differentiated adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were then partially purified and characterised. The growth-promoting factor(s) had apparent molecular weights of 10000 dalton and was sensitive both to heat and proteinase treatment. No inhibition for the factor(s) was achieved with defined anti-growth factor antibodies. In this study, differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts were shown. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. The growth factor(s) from gastric fibroblasts, which was distinct from various defined growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), transforming growth factor-alpha (TGF-alpha), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) may play an important role in the progression of scirrhous gastric cancer cells.
当癌细胞侵入胃黏膜下层时，硬癌性胃癌细胞会随着纤维化而迅速增殖。为了研究导致这种快速增殖的机制，我们检测了胃癌细胞与成纤维细胞之间的生长相互作用。我们使用了从硬癌或高分化腺癌建立的人胃癌细胞系。人成纤维细胞系则取自各种器官。通过计算癌细胞数量或测量癌细胞的[3H]胸腺嘧啶核苷掺入量来检测胃癌细胞与成纤维细胞之间的生长相互作用。胃成纤维细胞特异性地刺激了硬癌性胃癌细胞的生长，但对高分化腺癌细胞的生长没有刺激作用。然后对胃成纤维细胞产生的生长因子进行了部分纯化和鉴定。这种生长促进因子的表观分子量为10000道尔顿，对热和蛋白酶处理均敏感。使用特定的抗生长因子抗体未能对该因子产生抑制作用。在本研究中，显示了硬癌性和高分化胃癌细胞对原位成纤维细胞的不同反应。硬癌性胃癌的快速增殖应部分受原位成纤维细胞的控制。胃成纤维细胞产生的生长因子不同于各种特定的生长因子，如表皮生长因子（EGF）、碱性成纤维细胞生长因子（b-FGF）、转化生长因子-α（TGF-α）、角质形成细胞生长因子（KGF）、血管内皮生长因子（VEGF）、胰岛素样生长因子I（IGF-I）、肝细胞生长因子（HGF）、血小板衍生生长因子（PDGF）和转化生长因子β1（TGF-β1），它可能在硬癌性胃癌细胞的进展中起重要作用。
