Blood:血小板糖蛋白VI通过与癌细胞Galectin-3互作促进转移

2020-02-11 QQY MedSci原创

越来越多的证据表明,血小板在结肠癌和乳腺癌转移中起主要作用,但其潜在的分子机制仍不清楚。糖蛋白VI(GPVI)是一种胶原蛋白和纤维蛋白的血小板特异性受体,可通过免疫受体酪氨酸基础的激活模体(ITAM)信号触发血小板激活,进而调控多种功能,包括血小板黏附、聚集和促凝活性。GPVI被认为是一种安全的抗血栓靶点,因为它的抑制作用在动脉血栓形成模型中具有保护作用,且对止血作用很小。在本研究中,研究人员发现

越来越多的证据表明,血小板在结肠癌乳腺癌转移中起主要作用,但其潜在的分子机制仍不清楚。糖蛋白VI(GPVI)是一种胶原蛋白和纤维蛋白的血小板特异性受体,可通过免疫受体酪氨酸基础的激活模体(ITAM)信号触发血小板激活,进而调控多种功能,包括血小板黏附、聚集和促凝活性。

GPVI被认为是一种安全的抗血栓靶点,因为它的抑制作用在动脉血栓形成模型中具有保护作用,且对止血作用很小。在本研究中,研究人员发现小鼠血小板GPVI遗传缺陷可减少实验性和自发性结肠癌和乳腺癌细胞的转移。在血小板缺乏脾酪氨酸激酶Syk(Syk是ITAM信号级联中的重要成分)的小鼠中也观察到相似的结果。

体内外分析表明,小鼠及人类GPVI均支持血小板粘附于结肠癌和乳腺癌细胞。采用CRISPR/Cas9基因敲除技术发现半乳糖凝集素-3是GPVI在肿瘤细胞上的主要对应受体。

体内研究表明血小板GPVI和肿瘤细胞表达的半乳糖凝集素-3之间的相互作用利用了血小板中的ITAM信号元件,有利于肿瘤细胞的外渗。最后,研究人员还发现JAQ1 F(ab)2介导的GPVI的抑制可有效地破坏血小板与肿瘤细胞的相互作用和肿瘤的转移。

综上所述,本研究揭示了血小板促进结肠癌和乳腺癌细胞转移的新机制,提示GPVI或可成为抗转移治疗的靶点。

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    2020-02-13 yxch36
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    2020-02-13 ylz8405
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