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

癌细胞和成纤维细胞之间存在复杂的相互作用。在这项研究中，成纤维细胞对肺癌细胞的影响进行了检查。使用9个人肺癌细胞系和14个成纤维细胞系。将肺癌细胞与成纤维细胞条件培养液（CM）共孵育，MTT比色法检测CM对肺癌细胞生长的促进作用。CM对9株肺癌细胞系中的5株有促进生长作用，对EGE的反应相似。在来源于无癌症个体的肺组织的成纤维细胞中也观察到这种效应。CM同样促进人肺癌细胞移植到裸鼠的生长。在6例肺癌患者中，5例获得了具有促生长作用的成纤维细胞，其中5例观察到较早的广泛淋巴结转移。此外，肺癌细胞中酪氨酸特异性磷酸化被额外的EGF加速。25例肺癌手术患者中13例磷酸化加速。17例中6例为n_0，8例中7例为n_1和n_2。从这些发现中，肺癌组织中具有促生长作用的成纤维细胞的存在，以及肺癌细胞中酪氨酸特异性磷酸化被认为与广泛的淋巴结转移有关，并且肺癌细胞对成纤维细胞CM的特殊反应可以是肺癌患者预后的有用指标。

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.