title: Matrikines from basement membrane collagens: a new anti-cancer strategy.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: FRE CNRS/URCA 7369, Université de Reims Champagne Ardenne, UFR Médecine, 51 Rue Cognacq Jay, 51095 Reims Cedex, France; Laboratoire Central de Biochimie, CHU de Reims, France.
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Monboisse
authors.affiliation: FRE CNRS/URCA 7369, Université de Reims Champagne Ardenne, UFR Médecine, 51 Rue Cognacq Jay, 51095 Reims Cedex, France; Laboratoire Central de Biochimie, CHU de Reims, France.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Oudart
authors.affiliation: FRE CNRS/URCA 7369, Université de Reims Champagne Ardenne, UFR Médecine, 51 Rue Cognacq Jay, 51095 Reims Cedex, France; Laboratoire Central de Biochimie, CHU de Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ramont
authors.affiliation: FRE CNRS/URCA 7369, Université de Reims Champagne Ardenne, UFR Médecine, 51 Rue Cognacq Jay, 51095 Reims Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brassart-Pasco
authors.affiliation: FRE CNRS/URCA 7369, Université de Reims Champagne Ardenne, UFR Médecine, 51 Rue Cognacq Jay, 51095 Reims Cedex, France; Laboratoire Central de Biochimie, CHU de Reims, France. Electronic address: fmaquart@chu-reims.fr.
authors.forename: François Xavier
authors.initials: FX
authors.lastname: Maquart
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001485:Basement Membrane / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003094:Collagen / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D003094:Collagen
keywords: Angiogenesis; Cancer; Extracellular matrix; Matrikine; Preclinical trial