The Interaction of Platelets with Colorectal Cancer Cells Inhibits Tumor Growth but Promotes Metastasis
The Interaction of Platelets with Colorectal Cancer Cells Inhibits Tumor Growth but Promotes Metastasis
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DOI：
10.1158/0008-5472.can-19-1181
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发表时间：
2020-01-15
期刊：
影响因子：
11.2
通讯作者：
Panicot-Dubois, Laurence
中科院分区：
文献类型：
--
作者：
Plantureux, Lea;Mege, Diane;Panicot-Dubois, Laurence
血小板促进转移，然而，它们在肿瘤生长中的作用仍然存在争议。在这里，我们研究了血小板与结直肠肿瘤细胞相互作用的影响。血小板外渗到肿瘤微环境中，并以钙粘蛋白-6依赖的方式与肿瘤细胞相互作用。这种相互作用诱导血小板扩散，释放其颗粒内容物，并产生三种类型的微粒（iMP），表达血小板标志物，肿瘤标志物，或两者兼而有之。在结直肠癌组织标本中证实了iMP的存在。血小板显著减少肿瘤生长和增加瘤内巨噬细胞。这是由巨噬细胞通过趋化因子RANTES、MIF、CCL 2和CXCL 12的iMP募集以及通过IFN γ和IL 4激活其肿瘤细胞杀伤能力介导的，这导致肿瘤细胞以p21依赖性方式的细胞周期停滞。相反，在血流中，iMPs激活内皮细胞和血小板并诱导肿瘤细胞的上皮向间质转化，促进转移。总之，这些结果表明，根据环境，局部或血流，血小板和肿瘤之间的相互作用的后果可能会促进或防止cancer progression.Significance：肿瘤细胞与血小板的相互作用产生嵌合细胞外囊泡，通过激活肿瘤消除巨噬细胞抑制原发性肿瘤的生长，同时通过EMT和内皮激活促进转移。
Platelets promote metastasis, however, their role in tumor growth remains controversial. Here, we investigated the effect of platelet interactions with colorectal tumor cells. Platelets extravasated into the tumor microenvironment and interacted with tumor cells in a cadherin-6-dependent manner. The interaction induced platelet spreading, release of their granule content, and the generation of three types of microparticles (iMP) that expressed platelet markers, tumor markers, or both. The presence of iMPs was confirmed in colorectal cancer tissue specimens. Platelets significantly reduced tumor growth and increased intratumoral macrophages. This was mediated by iMP recruitment of macrophages via the chemoattractants RANTES, MIF, CCL2, and CXCL12 and activation of their tumor cell killing capacity through IFN gamma and IL4, which led to cell-cycle arrest of tumor cells in a p21-dependent manner. In contrast, in the bloodstream, iMPs activated endothelial cells and platelets and induced epithelial-to-mesenchymal transition of tumor cells, promoting metastasis. Altogether, these results indicate that depending on the environment, local or bloodstream, the consequences of the interactions between platelets and a tumor may promote or prevent cancer progression.Significance: Tumor cell interaction with platelets produces chimeric extracellular vesicles that suppress primary tumor growth by activating tumor-eliminating macrophages, while promoting metastasis through EMT and endothelial activation.