title: Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans.
abstract: Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were first evaluated in vitro on human and murine osteosarcoma cell lines. Different biological activities were studied: cell proliferation, cell adhesion and migration, matrix metalloproteinase expression. This in vitro study showed that only the OS-EPS 15 kDa derivative could inhibit the invasiveness of osteosarcoma cells with an inhibition rate close to 90%. Moreover, this derivative was potent to inhibit both migration and invasiveness of osteosarcoma cell lines; had no significant effect on their cell cycle; and increased slightly the expression of MMP-9, and more highly the expression of its physiological specific tissue inhibitor TIMP-1. Then, the in vivo experiments showed that the OS-EPS 15 kDa derivative had no effect on the primary osteosarcoma tumor induced by osteosarcoma cell lines but was very efficient to inhibit the establishment of lung metastases in vivo. These results can help to better understand the mechanisms of GAGs and GAG-like derivatives in the biology of the tumor cells and their interactions with the bone environment to develop new therapeutic strategies.
authors.affiliation: INSERM, UMR957, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 957, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Equipe Ligue Contre le Cancer 2012, Nantes 44035, France. dominique.heymann@sheffield.ac.uk.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: INSERM, UMR957, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 957, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Equipe Ligue Contre le Cancer 2012, Nantes 44035, France. ruizvela@usc.edu.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz-Velasco
authors.affiliation: INSERM, UMR957, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 957, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Equipe Ligue Contre le Cancer 2012, Nantes 44035, France. julie.chesneau@laposte.net.
authors.forename: Julie
authors.initials: J
authors.lastname: Chesneau
authors.affiliation: IFREMER, Institut Français de Recherche pour l'Exploitation de la Mer, Laboratoire EM<sup>3</sup>B Ecosystèmes Microbiens et Molécules Marines pour les Biotechnologies, BP21105, Nantes 44311, France. Jacqueline.Ratiskol@ifremer.fr.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ratiskol
authors.affiliation: IFREMER, Institut Français de Recherche pour l'Exploitation de la Mer, Laboratoire EM<sup>3</sup>B Ecosystèmes Microbiens et Molécules Marines pour les Biotechnologies, BP21105, Nantes 44311, France. Corinne.Sinquin@ifremer.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Sinquin
authors.affiliation: IFREMER, Institut Français de Recherche pour l'Exploitation de la Mer, Laboratoire EM<sup>3</sup>B Ecosystèmes Microbiens et Molécules Marines pour les Biotechnologies, BP21105, Nantes 44311, France. Sylvia.Colliec.Jouault@ifremer.fr.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Colliec-Jouault
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000737:chemistry; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006025:Glycosaminoglycans / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D018716:Molecular Mimicry; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; D011135:Polysaccharides, Bacterial; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: bone metabolism; bone remodeling; derivatives; exopolysaccharides; glycosaminoglycan; heparin-like; lung mestatases; osteosarcoma; sulfation