Growth-promoting effects of fibroblasts on lung cancer with nodal involvement and clinical application

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There are complicated interactions between cancer cells and fibroblasts. In this study, the effects of fibroblasts on lung cancer cells were examined. Nine cell lines of human lung cancer cells and 14 cell lines of fibroblasts were used. Lung cancer cells were incubated in conditioned medium (CM) of fibroblasts, and promotion of the growth of lung cancer cells by CM was examined in vitro by MTTcolorimetric assay. CM of fibroblasts promoted the growth of 5 of the 9 cell lines of lung cancer cells, and the responses to EGE were similar. This effect was observed also in fibroblasts derived from lung tissue of cancer-free individuals. CM similarly promoted the growth of human lung cancer cells transplanted to nude mouse. Extensive lymph node metastasis was observed relatively early in 5 of 6 lung cancer patients from whom fibroblasts with growth-promoting effects were obtained. Moreover, tyrosin-specific phosphorylation in lung cancer cells was accelerated by an additional EGF. Acceleration of the phosphorylation was observed in 13 of 25 operated cases of lung cancer. Six of 17 cases were n_0 and seven of 8 cases were n_1 and n_2. From these findings, the presence of fibroblasts with growth-promoting effects in the lung cancer tissue, and tyrosin-specific phoshorylation in lung cancer cells are considered to be related to extensive lymph node metastasis, and the special responses of lung cancer cells to CM of fibroblasts can be a useful index for prognosis of lung cancer patients.