Fiche publication
Date publication
août 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie
,
Dr MONBOISSE Jean-Claude
,
Pr RAMONT Laurent
,
Dr OUDART Jean-Baptiste
Tous les auteurs :
Monboisse JC, Oudart JB, Ramont L, Brassart-Pasco S, Maquart FX
Lien Pubmed
Résumé
BACKGROUND: Tumor microenvironment is a complex system composed of a largely altered extracellular matrix with different cell types that determine angiogenic responses and tumor progression. Upon the influence of hypoxia, tumor cells secrete cytokines that activate stromal cells to produce proteases and angiogenic factors. In addition to stromal ECM breakdown, proteases exert various pro- or anti-tumorigenic functions and participate in the release of various ECM fragments, named matrikines or matricryptins, capable to act as endogenous angiogenesis inhibitors and to limit tumor progression. SCOPE OF REVIEW: We will focus on the matrikines derived from the NC1 domains of the different constitutive chains of basement membrane-associated collagens and mainly collagen IV. MAJOR CONCLUSIONS: The putative targets of the matrikine control are the proliferation and invasive properties of tumor or inflammatory cells, and the angiogenic and lymphangiogenic responses. Collagen-derived matrikines such as canstatin, tumstatin or tetrastatin for example, decrease tumor growth in various cancer models. Their anti-cancer activities comprise anti-proliferative effects on tumor or endothelial cells by induction of apoptosis or cell cycle blockade and the induction of a loss of their migratory phenotype. They were used in various preclinical therapeutic strategies: i) induction of their overexpression by cancer cells or by the host cells, ii) use of recombinant proteins or synthetic peptides or structural analogues designed from the structure of the active sequences, iii) used in combined therapies with conventional chemotherapy or radiotherapy. GENERAL SIGNIFICANCE: Collagen-derived matrikines strongly inhibited tumor growth in many preclinical cancer models in mouse. They constitute a new family of anti-cancer agents able to limit cancer progression. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
Référence
Biochim Biophys Acta. 2014 Aug;1840(8):2589-98
