Elastin-derived peptides increase invasive capacities of lung cancer cells by post-transcriptional regulation of MMP-2 and uPA.

  • Platform LUXGEN - Micro-Array
June 01, 2012 By:
  • Toupance S
  • Brassart B
  • Rabenoelina F
  • Ghoneim C
  • Vallar L
  • Polette M
  • Debelle L
  • Birembaut P.

Elastin-rich lung extracellular matrix is largely remodeled during tumor invasion. Elastin degradation produces peptides displaying a wide range of biological activities. These elastin derived peptides (EP) interact with the elastin receptor complex (ERC) but also bind to alpha(V)beta(3) integrin and galectin-3. In this study, we explored the role of EP and their receptors in tumor progression of lung carcinomas. Non-invasive and invasive lung tumor cell lines were incubated in presence of kappa-elastin (kappaE) or with synthetic peptides displaying receptor-specific sequences (VGVAPG, GRKRK, AGVPGLGVG and AGVPGFGAG). Modified Boyden chamber assays revealed an increased invasive capacity of invasive cells induced by kappaE. EP treatment had no effect on cell proliferation but zymography analysis revealed an increase of pro-MMP-2 and uPA levels in the conditioned media of treated cells. Moreover, the active form of MMP-2 was increased in invasive cells. Interestingly, this regulation was not observed at the mRNA level and actinomycin D was unable to inhibit kappaE effects. We also observed that the regulation of proteases protein level following kappaE treatment was an early process detectable after 1 h. All these effects could not be inhibited by lactose and V14, two ERC antagonists, or by blocking antibodies against alpha(V)beta(3) integrin and galectin-3. Finally, VGVAPG and GRKRK failed to reproduce kappaE effects whereas nonapeptides partially mimicked them. These results demonstrate that treatment with EP up-regulates invasiveness of lung tumor cells via the release of proteolytic enzymes. This modulation involves post-transcriptional mechanisms and a nonapeptide-receptor different from the ERC, alpha(V)beta(3) integrin and galectin-3.

2012 Jun. Clin Exp Metastasis.29(5):511-22. Epub 2012 Mar 21.
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