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

肿瘤细胞和肿瘤基质细胞之间的正相互作用促进肿瘤生长。

基本信息

批准号：
11670567
负责人：
TAKIGUCHI Yuichi
金额：
$ 2.24万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670567/
关键词：
lung carcinoma tumor stroma fibroblast hepatocyte growth factor vascular endothelial growth factor gene therapy vascular endothelial growth factor 肺小細胞癌 HGF VEGF

项目摘要

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.

为了建立研究肿瘤与间质成纤维细胞相互作用的实验模型，本研究利用人小细胞肺癌细胞系Wa和小鼠成纤维细胞系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之间正交互作用的模型。2)W-fib与Wa体外共培养可明显提高Wa的植板率。W-fib还可通过缩短潜伏期而增强Wa的致瘤性; 4）Wa与W-fib体外共培养可产生高水平的肝细胞生长因子（HGF），并在培养后18 h达到高峰，在18 h达到高峰。随后在培养上清液中出现高水平的血管内皮生长因子（VEGF），在27小时达到峰值。单独的Wa或单独的W-fib不能在培养液中产生HGF或VEGF。5)HGF反义寡核苷酸阻断了VEGF的产生，并在体外抑制了Wa的成板效率。总之，在本模型中，肿瘤细胞和间质成纤维细胞之间存在正的相互作用。这种现象与基质成纤维细胞产生HGF和肿瘤细胞产生VEGF有关。