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

Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-913, Brazil

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA

Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland

Author to whom correspondence should be addressed.

^†

Equal contribution as first authors.

^‡

In memorian of E.O.K.

Cancers 2020, 12(6), 1353; https://doi.org/10.3390/cancers12061353

Received: 16 April 2020 / Revised: 14 May 2020 / Accepted: 22 May 2020 / Published: 26 May 2020

(This article belongs to the Collection Matrix Effectors and Cancer)

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Abstract

Although metastasis is the primary cause of death in patients with malignant solid tumors, efficient anti-metastatic therapies are not clinically available currently. Sulfated glycosaminoglycans from marine sources have shown promising pharmacological effects, acting on different steps of the metastatic process. Oversulfated dermatan sulfates from ascidians are 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 metastases 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 it efficiently prevented metastasis. Therefore, it may be a promising candidate for the development of a novel anti-metastatic drug. View Full-Text

Keywords: marine invertebrates; glycosaminoglycans; platelets; circulating tumor cells; circulating tumor microemboli; hematogenous metastasis

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MDPI and ACS Style

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. https://doi.org/10.3390/cancers12061353

AMA Style

Silva CFS, Motta JM, Teixeira FCOB, Gomes AM, Vilanova E, Kozlowski EO, Borsig L, Pavão MSG. Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction. Cancers. 2020; 12(6):1353. https://doi.org/10.3390/cancers12061353

Chicago/Turabian Style

Silva, Christiane F.S., Juliana M. Motta, Felipe C.O.B. Teixeira, Angélica M. Gomes, Eduardo Vilanova, Eliene O. Kozlowski, Lubor Borsig, and Mauro S.G. Pavão. 2020. "Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction" Cancers 12, no. 6: 1353. https://doi.org/10.3390/cancers12061353

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

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