Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction

Version 1 : Received: 17 May 2020 / Approved: 19 May 2020 / Online: 19 May 2020 (07:45:44 CEST)

A peer-reviewed article of this Preprint also exists.

Silva, C.F.S.; Motta, J.M.; Teixeira, F.C.O.B.; Gomes, A.M.; Vilanova, E.; Kozlowski, E.O.; Borsig, L.; Pavão, M.S.G. Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction. Cancers 2020, 12, 1353. Silva, C.F.S.; Motta, J.M.; Teixeira, F.C.O.B.; Gomes, A.M.; Vilanova, E.; Kozlowski, E.O.; Borsig, L.; Pavão, M.S.G. Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction. Cancers 2020, 12, 1353.

Abstract

Although metastasis is the primary cause of death on patients with malignant solid tumors, efficient antimetastatic therapies are not clinically available thus far. Sulfated glycosaminoglycans from marine sources have shown promising pharmacological effects, acting in different steps of the metastatic process. Oversulfated dermatan sulfate from ascidians is effective in preventing metastasis by inhibition of P-selectin, a platelet surface protein involved in the platelet-tumor cell emboli formation. We report in this work that the heparan sulfate isolated from the viscera of the ascidian Phallusia nigra drastically attenuates metastasis of colon carcinoma cells in mice. Our in vitro and in vivo assessments demonstrate that the P. nigra glycan has very low anticoagulant and antithrombotic activities and a reduced hypotension potential, although efficiently preventing metastasis. Therefore, it may be a promising candidate for the development of a novel anti-metastatic drug.

Keywords

marine invertebrates; glycosaminoglycans; platelets; circulating tumor cells; circulating tumor microemboli; hematogenic metastasis

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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