HUMAN-MELANOMA CELL-LINES DIFFER IN THEIR CAPACITY TO RELEASE ADP AND AGGREGATE PLATELETS
HUMAN-MELANOMA CELL-LINES DIFFER IN THEIR CAPACITY TO RELEASE ADP AND AGGREGATE PLATELETS
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DOI：
10.1111/j.1365-2141.1994.tb06736.x
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发表时间：
1994-08-01
影响因子：
6.5
通讯作者：
MCGREGOR, JL
中科院分区：
文献类型：
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作者：
BOUKERCHE, H;BERTHIERVERGNES, O;MCGREGOR, JL
在这项研究中，我们用三种不同的人黑色素瘤细胞系(M(1)DO，M(3)D，M(4)BE)研究了黑色素瘤细胞在ADP或凝血酶抑制剂存在或不存在的情况下诱导血小板聚集的不同能力。用免疫沉淀法、结合法和流式细胞术检测不同整合素(α(V)、β(3)、α(V)β(3)、α(IIb)、α(V)β(3))的表达水平。用ADP生物测定法和高效液相色谱法测定黑色素瘤细胞培养上清液中ADP的含量。M(3)Da诱导的血小板不可逆性聚集。如电子显微镜所示，与M(1)相反。这导致了一种缓慢的可逆聚集。M(4)是。不能诱导血小板聚集。在这两种情况下，M(3)Da。或M(1)Do，apyrase但不能抑制PPACK诱导的血小板聚集。抗α(V)β(3)单抗(LYP18)或多克隆抗体抑制血小板聚集。与M(1)DO、M(3)Da表面结合的LYP18分子数目相近。和M(4)是。细胞系。肿瘤细胞培养上清液中ADP的生物高效液相色谱检测显示，M(3)Da分泌的ADP浓度最高，其次是M(1)DO，而M(4)Be则未检测到ADP。这些结果表明，三种人黑色素瘤细胞系体外聚集能力的差异与整合素表达水平低无关，而与它们产生ADP的能力有关。人黑色素瘤细胞产生ADP可能是黑色素瘤-血小板相互作用的重要调节因子。
In this study we have investigated, using three different human melanoma cell lines (M(1)Do., M(3)Da., M(4)Be.), the varying capacity of melanoma cells to induce platelet aggregation in the presence or absence of inhibitors of ADP or thrombin. The expression levels of different integrins (alpha(v), beta(3), alpha(v) beta(3), alpha(IIb), alpha(v) beta(3)) were evaluated by immunoprecipitation, binding and now cytometry studies. The level of ADP in supernatants of melanoma cells were quantified by ADP bioassay and HPLC. Platelets were irreversibly aggregated by M(3)Da. as shown by electron microscopy, in contrast to M(1)Do. which induced a slow reversible aggregation. M(4)Be. did not induce platelet aggregation. In both cases, with M(3)Da. or M(1)Do., apyrase but not PPACK inhibited platelet induced aggregation. An anti-alpha(v) beta(3) monoclonal antibody (LYP18) or polyclonal antibody inhibited platelet aggregation. A similar number of LYP18 molecules bound to the surface of M(1)Do., M(3)Da. and M(4)Be. cell lines. Biological HPLC assays of ADP present in the supernatant of tumour cell lines showed the highest concentration of ADP to be secreted by M(3)Da., followed by M(1)Do., and none detected for M(4)Be. These results show that differences in in vitro aggregating potential of the three human melanoma cell lines are not related to low integrin expression levels but to their ability to generate ADP. Generation of ADP by human melanoma cells may act as important modulator of melanoma-platelet interactions.