Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans

Type Article
Date 2016-03
Language English
Author(s) Heymann Dominique1, Ruiz-Velasco Carmen1, Chesneau Julie1, Ratiskol Jacqueline2, Sinquin CorinneORCID2, Colliec-Jouault SylviaORCID2
Affiliation(s) 1 : INSERM, UMR957, Lab Physiopathol Resorpt Osseuse & Therapie Tumeu, Equipe Ligue Canc 2012, F-44035 Nantes, France.
2 : IFREMER, Lab Ecosyst Microbiens & Mol Marines Biotechnol E, BP21105, F-44311 Nantes, France.
Source Molecules (1420-3049) (Mdpi Ag), 2016-03 , Vol. 21 , N. 3 , P. -
DOI 10.3390/molecules21030309
WOS© Times Cited 18
Note This article belongs to the collection Bioactive Compounds
Keyword(s) exopolysaccharides, glycosaminoglycan, heparin-like, derivatives, sulfation, bone metabolism, bone remodeling, lung mestatases, osteosarcoma
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.
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Heymann Dominique, Ruiz-Velasco Carmen, Chesneau Julie, Ratiskol Jacqueline, Sinquin Corinne, Colliec-Jouault Sylvia (2016). Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans. Molecules, 21(3), -. Publisher's official version : , Open Access version :