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首页> 外文期刊>Thrombosis and Haemostasis: Journal of the International Society on Thrombosis and Haemostasis >Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model.
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Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model.

机译：肝素衍生的4-18单位寡糖在临床前人黑色素瘤转移模型中的抗迁移和抗转移作用。

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摘要

Heparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti-CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect. These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.
机译：肝素及其衍生物已显示抑制血管生成和转移形成。因此，我们调查了含有4至22个单体的肝素片段在体外对人黑素瘤细胞增殖，迁移和侵袭以及在SCID小鼠模型中体内转移潜能的影响。仅寡糖dp18对细胞增殖具有显着的抑制作用。相反，除dp8和dp22外，所有研究的寡糖均抑制细胞迁移。抗CD44v3抗体刺激细胞迁移和侵袭，寡糖dp4和dp18可以减弱这种作用。这些片段也抑制了肌球蛋白轻链磷酸酶的催化​​活性。此外，寡糖dp4和dp18减少了静脉注射人黑素瘤细胞的SCID小鼠中形成的肺集落数量，而dp22在这方面被证明是无效的。这些研究表明，肝素片段具有抗迁移和抗转移的潜力。这些片段缺乏肝素的止血作用，表明它们是抗癌治疗中潜在的特定抗肿瘤药。

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