Wang Yiqiang, Zhang Hongbo
Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China.
Thromb Res. 2008;123(2):324-30. doi: 10.1016/j.thromres.2008.06.021. Epub 2008 Aug 9.
Previous studies have suggested that platelets play a role in hematogenous metastasis of cancer cells by enhancing their survival in and extravasation from the bloodstream. We initiated studies to determine the effect of platelets on the proliferation of tumor cells.
Intact platelets or platelet subfractions were prepared and used for co-culture with various tumor cell lines of different major histocompatibility complex (MHC) backgrounds. Proliferation of tumor cells was monitored using a colorigenic method; flow cytometry was used to measure apoptosis or the cell cycle in L1210 cells.
Co-culture of platelets with tumor cells inhibited proliferation of tumor cells in an MHC-independent manner; soluble factors released from platelets as well as physical contact between platelets and tumor cells were involved. Cell-cycle analysis showed that platelets inhibited proliferation mainly through arrest of the cell cycle and inhibition of DNA synthesis. Neither cytotoxicity nor apoptosis mechanisms dominate in the platelet-induced inhibition of tumor cell proliferation.
We observed that murine platelets inhibit growth of tumor cells in vitro in an MHC-I-independent way, and this inhibition is not limited to specific tumor types, nor is it dependent on cytotoxicity or apoptotic pathways; rather it relies on impairment of the cell cycle.
先前的研究表明，血小板通过提高癌细胞在血液中的存活率和促进其从血液中渗出，在癌细胞的血行转移中发挥作用。我们开展了研究以确定血小板对肿瘤细胞增殖的影响。
制备完整血小板或血小板亚组分，并用于与不同主要组织相容性复合体（MHC）背景的各种肿瘤细胞系共培养。使用比色法监测肿瘤细胞的增殖；采用流式细胞术检测L1210细胞的凋亡或细胞周期。
血小板与肿瘤细胞共培养以不依赖MHC的方式抑制肿瘤细胞增殖；血小板释放的可溶性因子以及血小板与肿瘤细胞之间的物理接触均参与其中。细胞周期分析表明，血小板主要通过使细胞周期停滞和抑制DNA合成来抑制增殖。在血小板诱导的肿瘤细胞增殖抑制中，细胞毒性和凋亡机制均不起主导作用。
我们观察到，小鼠血小板以不依赖MHC-I的方式在体外抑制肿瘤细胞生长，这种抑制不限于特定肿瘤类型，也不依赖于细胞毒性或凋亡途径；相反，它依赖于细胞周期的损伤。
