Interleukin-1 beta and transforming growth factor-beta 3 cooperate to activate matrix metalloproteinase expression and invasiveness in A549 lung adenocarcinoma cells

Cancer Lett. 2012 Dec 28;325(2):220-6. doi: 10.1016/j.canlet.2012.07.009. Epub 2012 Jul 13.

Abstract

Cytokines present in the tumor microenvironment can promote the invasiveness and metastatic potential of cancer cells. We therefore investigated the effects of interleukin-1 beta (IL-1B) and transforming growth factor beta-3 (TGFB3) on the non-small cell lung carcinoma (NSCLC) cell line A549. We found that these cytokines synergistically activated matrix metalloproteinase (MMP)-1, MMP-3, and MMP-10 gene expression in these cells through mitogen-activated protein kinase (MAPK)-dependent pathways. Consistent with this, both cytokines stimulated epithelial to mesenchymal transition and MAPK-dependent invasion through Matrigel™. These studies identify IL-1B and TGFB3 as pro-invasive factors in NSCLC and potential therapeutic targets for tumor progression.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / pathology*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / enzymology
  • Cell Line, Tumor / pathology
  • Collagen
  • Drug Combinations
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Enzyme Induction / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-1beta / pharmacology*
  • Kidney Neoplasms / pathology
  • Laminin
  • Lung Neoplasms / pathology*
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 10 / biosynthesis*
  • Matrix Metalloproteinase 10 / genetics
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Matrix Metalloproteinase 3 / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Proteoglycans
  • Transforming Growth Factor beta3 / pharmacology*

Substances

  • Drug Combinations
  • Interleukin-1beta
  • Laminin
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Proteoglycans
  • TGFB3 protein, human
  • Transforming Growth Factor beta3
  • matrigel
  • Collagen
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 10
  • Matrix Metalloproteinase 1