Positive interaction between tumor cells and tumor stromal cells for tumor growth.

为了建立研究肿瘤与其间质成纤维细胞相互作用的实验模型，本研究利用了人小细胞肺癌细胞系Wa和小鼠成纤维细胞细胞系W-fib。结果：1)建立了体外和体内研究肿瘤细胞与成纤维细胞正相互作用的模型。2) W-fib与Wa体外共培养明显提高了Wa的电镀效率。从成纤维细胞释放的一些可溶性因子被推测是造成这种效果的原因。3) W-fib通过缩短小鼠的潜伏期，增强了Wa的致瘤性。4) Wa和W-fib体外共培养产生高水平的肝细胞生长因子（HGF），在培养后18小时达到峰值，其次是高水平的血管内皮生长因子（VEGF），在培养上料中27小时达到峰值。然而，单独的Wa或单独的W-fib不能在培养基中促进HGF或VEGF。5)一个靶向HGF的反义寡核苷酸阻断了VEGF的产生，从而抑制了Wa的体外镀效率。总之，在这里的模型中，肿瘤细胞和它们的间质成纤维细胞之间的正相互作用被证实。这种现象与间质成纤维细胞产生HGF和肿瘤细胞产生VEGF有关。

To establish an experimental model for investigating interaction between tumor and its stromal fibroblasts, the research utilized a human small cell lung carcinoma cell line, Wa, and a mouse fibroblast cell line, W-fib.As results, 1) The model, in which a positive reciprocal interaction between tumor cells and fibroblasts is investigated both in vitro and in vivo, was established. 2) In vitro co-culture of W-fib with Wa obviously enhanced plating efficiency of the Wa. Some soluble factors released from the fibroblasts were speculated to cause the effect.3) The W-fib also enhanced tumorigenesity of the Wa when inoculated into nude mice, by reducing incubation period.4) In vitro co-culture of Wa and W-fib produced high level hepatocyte growth factor (HGF) with a peak at 18 hours after the culture, followed by high level vascular endothelial growth factor (VEGF) with a peak at 27 hours in the culture supematant. The Wa alone or W-fib alone, however, did not prodece HGF or VEGF in the culture medium. 5) An antisense oligo DNA targeting HGF blocked the production of VEGF, and, thereafter, suppresed plating efficinecy of the Wa, in vitro.In conclusion, in the model presented here, a positive reciprocal interaction between the tumor cells and their stromal fibroblasts was demonstrated. This phenomenon was associated with HGF production by the stromal fibroblasts and VEGF production by the tumor cells.