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

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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.