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Cousin R, Groult H, Manseur C, et al. A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis. Mar Drugs. 2021;19(10)doi: 10.3390/md19100546.
Cousin, R., Groult, H., Manseur, C., Ferru-Clément, R., Gani, M., Havret, R., Toucheteau, C., Prunier, G., Colin, B., Morel, F., Piot, J. M., Lanneluc, I., Baranger, K., Maugard, T., & Fruitier-Arnaudin, I. (2021). A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis. Marine drugs, 19(10), . https://doi.org/10.3390/md19100546
Cousin, Rémi, et al. "A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis." Marine drugs vol. 19,10 (2021). doi: https://doi.org/10.3390/md19100546
Cousin R, Groult H, Manseur C, Ferru-Clément R, Gani M, Havret R, Toucheteau C, Prunier G, Colin B, Morel F, Piot JM, Lanneluc I, Baranger K, Maugard T, Fruitier-Arnaudin I. A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis. Mar Drugs. 2021 Sep 28;19(10). doi: 10.3390/md19100546. PMID: 34677445; PMCID: PMC8539239.
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Mar Drugs. 2021 Sep 28;19(10). doi: 10.3390/md19100546.

A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis.

Marine drugs

Rémi Cousin, Hugo Groult, Chanez Manseur, Romain Ferru-Clément, Mario Gani, Rachel Havret, Claire Toucheteau, Grégoire Prunier, Béatrice Colin, Franck Morel, Jean-Marie Piot, Isabelle Lanneluc, Kévin Baranger, Thierry Maugard, Ingrid Fruitier-Arnaudin

Affiliations

  1. BCBS Group (Biotechnologies et Chimie des Bioressources pour la Santé), Laboratoire Littoral Environnement et Sociétés, La Rochelle University, UMR CNRS 7266, 17000 La Rochelle, France.
  2. Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, Poitiers University, LITEC EA 4331, 86073 Poitiers, France.
  3. Aix-Marseille University, CNRS, INP, Inst Neurophysiopathol, 13385 Marseille, France.

PMID: 34677445 PMCID: PMC8539239 DOI: 10.3390/md19100546

Abstract

Sugar-based molecules such as heparins or natural heparan sulfate polysaccharides have been developed and widely studied for controlling heparanase (HPSE) enzymatic activity, a key player in extracellular matrix remodelling during cancer pathogenesis. However, non-enzymatic functions of HPSE have also been described in tumour mechanisms. Given their versatile properties, we hypothesized that sugar-based inhibitors may interfere with enzymatic but also non-enzymatic HPSE activities. In this work, we assessed the effects of an original marine λ-carrageenan derived oligosaccharide (λ-CO) we previously described, along with those of its native counterpart and heparins, on cell viability, proliferation, migration, and invasion of MDA-MB-231 breast cancer cells but also of sh-MDA-MB-231 cells, in which the expression of HPSE was selectively downregulated. We observed no cytotoxic and no anti-proliferative effects of our compounds but surprisingly λ-CO was the most efficient to reduce cell migration and invasion compared with heparins, and in a HPSE-dependent manner. We provided evidence that λ-CO tightly controlled a HPSE/MMP-14/MMP-2 axis, leading to reduced MMP-2 activity. Altogether, this study highlights λ-CO as a potent HPSE "modulator" capable of reducing not only the enzymatic activity of HPSE but also the functions controlled by the HPSE levels.

Keywords: MDA-MB-231; MMP-14; breast cancer; heparanase; heparin; metalloproteinase; oligosaccharide; polysaccharide; shRNA; λ-carrageenan

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