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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 5/2012

01-06-2012 | Research Paper

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

Authors: Simon Toupance, Bertrand Brassart, Fanja Rabenoelina, Christelle Ghoneim, Laurent Vallar, Myriam Polette, Laurent Debelle, Philippe Birembaut

Published in: Clinical & Experimental Metastasis | Issue 5/2012

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Abstract

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 αVβ3 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 (κE) 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 κE. 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 κE effects. We also observed that the regulation of proteases protein level following κE 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 αVβ3 integrin and galectin-3. Finally, VGVAPG and GRKRK failed to reproduce κE 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, αVβ3 integrin and galectin-3.
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Metadata
Title
Elastin-derived peptides increase invasive capacities of lung cancer cells by post-transcriptional regulation of MMP-2 and uPA
Authors
Simon Toupance
Bertrand Brassart
Fanja Rabenoelina
Christelle Ghoneim
Laurent Vallar
Myriam Polette
Laurent Debelle
Philippe Birembaut
Publication date
01-06-2012
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 5/2012
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-012-9467-3

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