Transforming Growth Factor-Beta Produced by Non-small Cell Lung Cancer Cells Contributes to Lung Fibroblast Contractile Phenotype

Anticancer Res. 2018 Apr;38(4):2007-2014. doi: 10.21873/anticanres.12439.

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.

Keywords: Lung cancer; cancer-associated fibroblast; collagen gel contraction; fibroblast; transforming growth factor.

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Communication / physiology
  • Cell Line, Tumor
  • Collagen / pharmacology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Phenotype
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Collagen