Pathophysiological significance of platelets on cancer invasion, proliferation, and angiogenesis

据报道，血小板可以帮助许多癌症形成血液转移。然而，其机制尚未完全阐明。近年来，一些癌细胞释放的IL-8被认为是促进血管生成和肿瘤侵袭增殖的重要细胞因子之一。在本研究中，我们发现血小板与人胰腺腺癌细胞MIA PaCa-2共孵生后可以被激活，并以血小板数量依赖的方式增强癌细胞对IL-8的释放。Northern blot分析显示，在血小板存在的情况下，MIA PaCa-2对IL-8 mRNA的表达也强烈上调。肿瘤细胞与凝血酶活化的血小板上清共孵育可轻微增强IL-8的释放。然而，剩余的脱颗粒血小板引起IL-8产生的更大增强。此外，在双腔培养中，与血小板在同一腔室中培养的MIA PaCa-2细胞比那些被膜屏障阻止血小板直接接触的细胞诱导了更多的IL-8的产生。此外，固定的、凝血酶激活的血小板显著增强MIA PaCa-2细胞释放IL-8，尽管固定的、未刺激的血小板并没有增强IL-8的产生。最后，这里测试的所有胰腺癌细胞表面粘附至少一个血小板的比例为70 - 90%，粘附三个或更多血小板的比例为30 - 50%。这些发现表明，血小板可能通过直接接触肿瘤细胞参与肿瘤的进展，以及活化血小板通过增强肿瘤细胞释放IL-8而衍生的可溶性因子。

It has been reported that platelets could help the formation of hematogenous metastasis in many cancers. However, the mechanism is not completely elucidated. Recently, IL-8, released by some cancer cells, has been considered to be one of important caytokines to promote angiogenesis as well as cancer invasion and proliferation. In the present study, we have shown that platelets could become activated after the co-incubation with human pancreatic adenocarcinoma cells MIA PaCa-2 and enhanced IL-8 release by cancer cells in the platelet number dependent manner. Northern blot analysis revealed that the expression of IL-8 mRNA by MIA PaCa-2 was also strongly upregulated in the presence of platelets. The co-incubation of tumor cells with the supernatant from thrombin-activated platelets resulted in a slight enhancement of IL-8 release. However, remaining degranulated platelets caused much greater enhancement in IL-8 production. Furthermore, MIA PaCa-2 cells cultured with platelets in the same chamber induced much more production of IL-8 than those cultured with platelets prevented from direct contact by a membrane barrier in the double chamber culture well study. In addition, fixed, thrombin-activated platelets significantly enhanced IL-8 release by MIA PaCa-2 cells, although fixed, unstimulated-platelets did not enhance the production of IL-8. Finally, all of pancreatic cancer cells tested here adhered to at least one platelet on their surface at 70 to 90%, and adhered to three or more platelets at 30 to 50%. These findings suggest that platelets could be involved in the tumor progression by the direct cantact to tumor cells as well as soluble factors derived from activated platelets through the enhancement of IL-8 release by tumor cells.