Transforming growth factor-beta produced by non-small cell lung cancer cells contributes to lung fibroblast contractile phenotype

Abstract

Background/Aim: Fibroblasts can alter the extracellular matrix (ECM), contributing to cancer progression by providing a scaffold for cancer cells. The influence of lung cancer cells (LCCs) on lung fibroblast-mediated ECM alteration is not well understood. Materials and Methods: After incubation in serum-free medium, LCC- or fibroblast-conditioned media were collected. The ECM alteration was assessed by collagen gel contraction assay. Results: Both LCC-conditioned medium and exogenous transforming growth factor (TGF)-β1 increased collagen gel contraction by lung fibroblasts. TGF-β1 was produced in LCC-conditioned media at approximately 2 ng/ml. SB431542, a specific TGF-β receptor kinase inhibitor, partially inhibited the collagen gel contraction that had been increased by LCC-conditioned media. Lung fibroblast-conditioned medium stimulated TGF-β1 production from LCCs, whereas LCC-conditioned medium decreased fibroblast survival and α-smooth muscle actin expression by fibroblasts. Conclusion: Interaction between LCCs and lung fibroblasts through TGF-β signaling induces fibroblasts to assume the contractile phenotype and may contribute to cancer progression.