Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
J Cell Mol Med. 2010 Apr;14(4):833-9. doi: 10.1111/j.1582-4934.2010.01040.x. Epub 2010 Jan 30.
There is growing evidence that the signal pathway between hepatocyte growth factor (HGF) and its receptor c-Met plays an important role in the development of lung cancer, although the specificity of such role is to be clarified. It seems clear that the HGF/c-Met signal contributes to the metastasis of cancer cells to the lung by stimulating the hyperproduction and overactivation of cytokines and enzymes, e.g. HGF, vascular endothelial growth factor and matrix metalloproteases. The HGF/c-Met signal may act as the candidate responsible for the development of epidermal growth factor receptor (EGFR) kinase inhibitor resistance. Experimental evidence showed that the combination of both EGFR and c-Met inhibitors had synergetic or additive therapeutic effects on lung cancer. Although the mechanism of interaction between HGF/c-Met and transforming growth factor-a/EGFR remains unclear, the cross-talk and balance between those two signal pathways are critical and necessary in the development of new therapies for lung cancer.
越来越多的证据表明，肝细胞生长因子（HGF）与其受体 c-Met 之间的信号通路在肺癌的发展中起着重要作用，尽管其特异性尚待阐明。似乎很清楚的是，HGF/c-Met 信号通过刺激细胞因子和酶（例如 HGF、血管内皮生长因子和基质金属蛋白酶）的过度产生和过度激活，促进癌细胞向肺部转移。HGF/c-Met 信号可能作为负责表皮生长因子受体（EGFR）激酶抑制剂耐药性发展的候选者。实验证据表明，EGFR 和 c-Met 抑制剂的联合使用对肺癌具有协同或相加的治疗效果。尽管 HGF/c-Met 和转化生长因子-α/EGFR 之间的相互作用机制尚不清楚，但这两个信号通路之间的交叉对话和平衡对于开发肺癌的新疗法至关重要。
