Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in
tumor growth, invasion and
metastasis, however, the underling mechanisms remain unclear. In the present study, we investigated the role of CAFs on the metastatic potential of
lung cancer cells. The stromal fibroblasts we isolated from
lung cancer tissues presented CAFs characteristics with high levels of α-smooth muscle actin (α-SMA) and fibroblast-activating
protein (FAP). Our data showed that the
conditioned medium from cultured CAFs (CAF-CM) dramatically enhanced migration and invasion of
lung cancer cells. CAF-CM induced epithelial-mesenchymal transition (EMT) by regulating the expression of EMT-associated markers
E-cadherin and
vimentin, and also modulated
metastasis-related genes MMP-2 and
VEGF both in vitro and in vivo. Further mechanistic studies demonstrated that CAFs enhanced the metastatic potential of
lung cancer cells by secreting
IL-6, subsequently activating of JAK2/STAT3 signaling pathway. Additionally, the inhibition of IL-6/STAT3 signaling pathway by
IL-6 neutralizing antibody or specific inhibitors of JAK2/STAT3 reversed CAF-CM induced EMT and migration of
lung cancer cells. Taken together, these findings revealed a novel mechanism that CAFs induced EMT and promoted
metastasis of
lung cancer cells through the IL-6/STAT3 signaling pathway.