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.
Highlights
Metastasis is a multi-step process by which cells from a primary tumor invade the adjacent extracellular matrix, reach the blood or lymphatic vessels, travel through circulation and extravasate the vessel wall to invade a distant tissue and form secondary tumors [1]
In this study, using mouse models we demonstrate that PNH can prevent lung metastasis of colon carcinoma cells by inhibiting the formation of circulating tumor microemboli (CTM)
We assessed whether has cytotoxic effects on the MC-38 colon carcinoma cell line using an MTT assay
Summary
Metastasis is a multi-step process by which cells from a primary tumor invade the adjacent extracellular matrix, reach the blood or lymphatic vessels, travel through circulation and extravasate the vessel wall to invade a distant tissue and form secondary tumors [1]. Tumor cells release cytokines in the bloodstream that activate platelets and the coagulation system [2]. Many glycoproteins at the surface of circulating tumor cells (CTCs) exhibit a specific epitope described as sialyl-Lewis X (or sialyl-Lewis A). These epitopes are recognized and bind to P-selectin expressed on the membrane of activated platelets, which lead to the formation of a platelet cloak around CTCs. platelet and tumor cell interaction is reinforced by fibrin accumulation around these cloaks, originating a circulating tumor microemboli (CTM) [3].
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