Involvement of phospholipase C signaling in melanoma cell-induced endothelial junction disassembly
Involvement of phospholipase C signaling in melanoma cell-induced endothelial junction disassembly
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DOI：
10.2741/1643
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Dong, C
中科院分区：
文献类型：
--
作者：
Peng, HH;Hodgson, L;Dong, C
在这项研究中，我们报告了磷脂酶C（PLC）介导的机制，重新分配内皮细胞间粘附连接的黑色素瘤细胞与内皮细胞的接触。我们证明了黑色素瘤细胞与人脐静脉内皮细胞（HUVEC）接触通过PLC-IP 3途径触发快速内皮[Ca 2 +]（i）反应。此外，血管内皮（VE）-钙粘蛋白免疫染色模式的变化证明了与黑色素瘤细胞接触后内皮粘附连接的改变。PLC抑制剂U 73122显示出显著减少[Ca 2 +] i反应并减少黑素瘤细胞诱导的VE-钙粘蛋白重组的发生。此外，抑制PLC减弱黑色素瘤细胞的跨内皮迁移。然而，黑色素瘤细胞相关的VE-钙粘蛋白的分解是不敏感的磷脂酰肌醇-3-激酶（PI 3 K）的抑制剂Ly 294002，而PI 3 K的抑制导致黑色素瘤细胞的迁移减少。总之，我们的研究结果表明，通过诱导PLC-Ca 2+信号通路，黑色素瘤细胞破坏EC连接，破坏内皮细胞，促进肿瘤细胞的跨血管归巢。
In this study, we report a phospholipase C ( PLC)mediated mechanism for the redistribution of interendothelial adherens junctions in response to melanoma cell contacts with the endothelium. We demonstrated that contact of melanoma cells to human umbilical vein endothelial cells ( HUVEC) triggered rapid endothelial [Ca2+](i) response through PLC-IP3 pathway. In addition, alternation of endothelial adherens junctions following contact of melanoma cells was evidenced by the changes in immunological staining patterns of vascular endothelial (VE)-cadherin. A PLC inhibitor, U73122 was shown to significantly diminish [ Ca2+] i response and reduce the occurrence of melanoma cell - induced VE-cadherin reorganization. Moreover, inhibition of PLC attenuated melanoma cell transendothelial migration. However, melanoma cell-associated VE-cadherin breakdown was not sensitive to Ly294002, an inhibitor of phosphatidylinositol-3- kinase (PI3K), whereas inhibition of PI3K resulted in a reduction of melanoma cell transmigration. Taken together, our findings implicate that by inducing the PLC-Ca2+ signaling pathway, melanoma cells disrupt EC junctions to breach the endothelium and promote transvascular homing of tumor cells.