Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6.
Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6.
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血小板释放通过抑制KLF6表达促进肝癌细胞增殖
DOI：
10.1038/s41598-017-02801-1
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发表时间：
2017-06-21
影响因子：
4.6
通讯作者：
Ming ZY
中科院分区：
文献类型：
--
作者：
He AD;Xie W;Song W;Ma YY;Liu G;Liang ML;Da XW;Yao GQ;Zhang BX;Gao CJ;Xiang JZ;Ming ZY
原发性肿瘤微环境中的血小板在肿瘤进展的调节中起着至关重要的作用，但其潜在的机制尚不清楚。在这里，我们报道血小板释放物在体外和体内对肝细胞癌（HCC）细胞具有增殖作用。这种作用依赖于HCC细胞中KLF6表达的减少。与血小板或血小板颗粒孵育后，SMMC.7721和HepG2细胞增殖明显增加，凋亡明显减少。然而，当再悬活化血小板颗粒耗尽释放物孵育癌细胞时，未观察到任何效果。血小板的释放也增加了细胞周期S期和G2/M期的HCC细胞数量，减少了G0/G1期的细胞数量。此外，敲低KLF6表达可显著降低血小板介导的肝癌生长增强。此外，TGF-β受体抑制剂SB431542阻断TGF-β信号通路可抵消血小板对肝癌细胞KLF6表达和增殖的影响。基于这些发现，我们认为血小板释放物，尤其是TGF-β，通过降低KLF6的表达，促进SMMC.7721和HepG2细胞的增殖。这一发现为预防和治疗肝细胞癌确定了一个潜在的新的治疗靶点。
Platelets in the primary tumor microenvironment play crucial roles in the regulation of tumor progression, but the mechanisms underlying are poorly understood. Here, we report that platelet releasates exerted a proliferative effect on hepatocellular carcinoma (HCC) cells bothin vitroandin vivo. This effect depended on a reduction of KLF6 expression in HCC cells. After incubation with either platelets or platelet granule contents, SMMC.7721 and HepG2 cells exhibited significant increases in proliferation and decreases in apoptosis. However, no effect was observed when incubating cancer cells with resuspended activated platelet pellet which exhausted of releasates. Platelet releasates also increased the population of HCC cells in the S and G2/M phases of the cell cycle and reduced the cell population in the G0/G1 phase. Moreover, knocking down KLF6 expression significantly diminished the platelet-mediated enhancement of HCC growth. In addition, blocking TGF-β signaling with the TGF-β receptor inhibitor SB431542 counteracted the effect of platelets on KLF6 expression and proliferation of HCC cells. Based on these findings, we conclude that platelet releasates, especially TGF-β, promote the proliferation of SMMC.7721 and HepG2 cells by decreasing expression of KLF6. This discovery identifies a potential new therapeutic target for the prevention and treatment of hepatocellular carcinoma.