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

• Published in: Marine drugs Vol. 19; no. 10; p. 546
• Main Authors: Cousin, Rémi, Groult, Hugo, Manseur, Chanez, Ferru-Clément, Romain, Gani, Mario, Havret, Rachel, Toucheteau, Claire, Prunier, Grégoire, Colin, Béatrice, Morel, Franck, Piot, Jean-Marie, Lanneluc, Isabelle, Baranger, Kévin, Maugard, Thierry, Fruitier-Arnaudin, Ingrid
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.09.2021; MDPI
• Subjects: Angiogenesis; Animals; Anticoagulants; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Aquatic Organisms; Autophagy; Biochemistry; Biochemistry, Molecular Biology; Breast cancer; Breast Neoplasms; Cancer; Cancer therapies; Carbon monoxide; Carrageenan; Carrageenan - chemistry; Carrageenan - pharmacology; Cell adhesion & migration; Cell Line, Tumor - drug effects; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell viability; Cells; Cellular Biology; Chemotherapy; Cytotoxicity; Enzymatic activity; Enzyme activity; Enzymes; Extracellular; Extracellular matrix; Female; Gelatinase A; Glucuronidase - metabolism; Heparan sulfate; heparanase; Heparin; Human performance; Humans; Inhibitory Concentration 50; Invasiveness; Life Sciences; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase 2 - metabolism; Matrix metalloproteinases; Metabolism; metalloproteinase; Metastasis; Molecular weight; Multiple myeloma; oligosaccharide; Oligosaccharides; Pathogenesis; polysaccharide; Polysaccharides; Proliferation; Rhodophyta; Saccharides; Sugar; Tumors; λ-carrageenan; heparin; oligosaccharide; λ-carrageenan; polysaccharide; shRNA; metalloproteinase; MMP-14; breast cancer; heparanase; MDA-MB-231
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md19100546

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.