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Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions.

Abstract : The substrate of matrix metalloproteinase 11 (MMP11) remains unknown. We have recently shown that MMP11 is a negative regulator of adipogenesis, able to reduce and even to revert mature adipocyte differentiation. Here, we have used mouse 3T3L1 cells and human U87MG and SaOS cells to show that MMP11 cleaves the native alpha3 chain of collagen VI, which is an adipocyte-related extracellular matrix component. It is known that extracellular proteolytic processing of this chain is required for correct collagen VI folding. Interestingly, MMP11-deficient fat tissue is less cohesive and exhibits collagen VI alteration, dramatic adipocyte plasma and basement membrane abnormalities and lipid leakage. MMP11 is thus required for correct collagen VI folding and therefore for fat tissue cohesion and adipocyte function. Both MMP11 and collagen VI favor tumor progression. Similar spatio-temporal overexpression at the adipocyte-cancer cell interface has been reported for the two proteins. MMP11-dependent collagen VI processing might therefore be expected to occur during malignancy. Accordingly, collagen VI no longer delineates adipocytes located at the invasive front of breast carcinomas. In conclusion, the native alpha3 chain of collagen VI constitutes a specific MMP11 substrate. This MMP11 collagenolytic activity is functional in fat tissue ontogenesis as well as during cancer invasive steps.
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https://www.hal.inserm.fr/inserm-00350819
Contributor : Maité Peney <>
Submitted on : Tuesday, February 3, 2009 - 3:12:59 PM
Last modification on : Thursday, April 23, 2020 - 2:26:26 PM

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Elena Motrescu, Sandra Blaise, Nicolas Etique, Nadia Messaddeq, Marie-Pierre Chenard, et al.. Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions.. Oncogene, Nature Publishing Group, 2008, 27 (49), pp.6347-55. ⟨10.1038/onc.2008.218⟩. ⟨inserm-00350819⟩

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