title: [Matrikines: a new anticancer therapeutic                                     strategy].
abstract: Tumor microenvironment is a complex system composed of a largely altered                               extracellular matrix (ECM) with different cell types that determine                               the angiogenic response. Upon the influence of hypoxia, tumor cells                               secrete cytokines that activate stromal cells to produce proteases and                               angiogenic factors. The proteases degrade the stromal ECM and                               participate in the release of various ECM fragments, named matrikines                               or matricryptins, capable to control tumor invasion and metastasis                               dissemination. 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. The putative                               targets of the matrikine action are the proliferation and invasive                               properties of tumor or inflammatory cells, and the angiogenic and                               lymphangiogenic responses. For example, canstatin, tumstatin and                               tetrastatin, respectively derived from the NC1 domains of α2, α3 and                               α4 chains of collagen IV, inhibit in vivo tumor                               growth in various experimental cancer models. Their anti-cancer                               activity comprises an anti-proliferative effect on tumor cells and on                               endothelial cells by induction of cell apoptosis or cell cycle                               blockade and the induction of a loss of their migratory phenotype.                               Matrikines constitute a new family of potent anticancer agents that                               could be used under various 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. These matrikines                               could be used in combination with conventional chemotherapy or                               radiotherapy to limit tumor progression.
authors: FRE CNRS/URCA 3481, Université Reims Champagne Ardenne, UFR Médecine, 51 Rue Cognacq-Jay, 51095 Reims Cedex, France. jc.monboisse@univ-reims.fr
authors: Jean Claude
authors: JC
authors: Monboisse
authors: Karine
authors: K
authors: Sénéchal
authors: Jessica
authors: J
authors: Thevenard
authors: Laurent
authors: L
authors: Ramont
authors: Sylvie
authors: S
authors: Brassart-Pasco
authors: François-Xavier
authors: FX
authors: Maquart
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002986:Clinical Trials as Topic; D003094:Collagen / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D003094:Collagen