ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

J. Dubail, F. Kesteloot, C. Deroanne, P. Motte, V. Lambert, J.-M. Rakic, C. Lapière, B. Nusgens, A. Colige

ABSTRACT

ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ADAMTS-2 is also able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. Dephosphorylation of Erk1/2 and MLC largely precedes the ADAMTS-2 induced morphological alterations. In 3-D culture models, ADAMTS-2 strongly reduced branching of capillary-like structures formed by endothelial cells and their long-term maintenance and inhibited vessels formation in embryoid bodies (EB). Growth and vascularization of tumors formed in nude mice by HEK 293-EBNA cells expressing ADAMTS-2 were drastically reduced. A similar anti-tumoral activity was observed when using cells expressing recombinant deleted forms of ADAMTS-2, including catalytically inactive enzyme. Nucleolin, a nuclear protein also found to be associated with the cell membrane, was identified as a potential receptor mediating the antiangiogenic properties of ADAMTS-2. More... »

PAGES

4213-4232

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00018-010-0431-6

DOI

http://dx.doi.org/10.1007/s00018-010-0431-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018879618

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20574651


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