Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity
Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity
复制标题
血小板和纤维蛋白原相互促进，保护肿瘤细胞免受自然杀伤细胞毒性的影响
DOI：
10.1111/j.1349-7006.2009.01115.x
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发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Zeng, Xianlu
中科院分区：
文献类型：
--
作者：
Zheng, Sheng;Shen, Jian;Zeng, Xianlu
血小板和纤维蛋白原在保护肿瘤细胞免受自然杀伤细胞毒害中的作用已经讨论了20多年。然而，他们在这一过程中的确切角色和关系仍不清楚。在这项研究中，我们发现肿瘤细胞更喜欢与纤维蛋白原黏附，而不是与血小板黏附，而且纤维蛋白原可以增强肿瘤细胞与血小板的黏附。β-3整合素在纤维蛋白原增强B16F10与血小板的黏附中起重要作用。在凝血酶的存在下，纤维蛋白原在肿瘤细胞周围形成致密的纤维蛋白(原)层。肿瘤细胞可以诱导血小板聚集并形成凝血酶。血小板和凝血酶一样，可以帮助纤维蛋白原保护肿瘤细胞免受与自然杀伤细胞的致命接触和自然杀伤细胞的细胞毒性。水飞蓟素是一种凝血酶的特异性抑制剂，可以逆转血小板对纤维蛋白原的作用，从而阻断自然杀伤细胞的细胞毒作用。我们的结果表明，纤维蛋白原有助于血小板与肿瘤细胞黏附，而血小板反过来又通过形成凝血酶促进更多的纤维蛋白原聚集在肿瘤细胞周围。它们在保护肿瘤细胞免受自然杀伤细胞毒性方面相互促进。(《癌症科学》2009；100：859-865)
The functions of platelets and fibrinogen in protecting tumor cells from natural killer cytotoxicity have been discussed for more than 20 years. However, their exact roles and relationships in the process are still not clear. In this study, we show that tumor cells prefer to adhere to fibrinogen than to platelets, and fibrinogen can enhance the adhesion of tumor cells to platelets. β3 integrin plays an important role in the adhesion of B16F10 to platelets enhanced by fibrinogen. In the presence of thrombin, fibrinogen forms dense fibrin(ogen) layers around tumor cells. Tumor cells can induce platelets to aggregate and form thrombin. Platelets, as well as thrombin, can help fibrinogen protect tumor cells from lethal contact with natural killer cells and natural killer cytotoxicity. Hirudin, a specific inhibitor of thrombin, can reverse the effect of platelets on fibrinogen in blocking natural killer cytotoxicity. Our results suggest that fibrinogen helps platelets to adhere to tumor cells, and platelets in turn promote more fibrinogen to aggregate around tumor cells by forming thrombin. They facilitate each other in protecting tumor cells from natural killer cytotoxicity. (Cancer Sci 2009; 100: 859–865)