Involvement of p38α mitogen-activated protein kinase in lung metastasis of tumor cells
Involvement of p38α mitogen-activated protein kinase in lung metastasis of tumor cells
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DOI：
10.1074/jbc.m604371200
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发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Kasuya, Yoshitoshi
中科院分区：
文献类型：
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作者：
Matsuo, Yuji;Amano, Shinya;Kasuya, Yoshitoshi
为了研究p38丝裂原活化蛋白激酶（p38）活性在转移过程中的作用，我们对p38 α(+/-)小鼠进行了体内转移实验。经静脉注射p38 α(-/-)小鼠肺肿瘤细胞菌落数较野生型（WT）小鼠明显减少。另一方面，皮下肿瘤细胞移植后肿瘤体积的时间依赖性增加在WT和p38 α(+/-)小鼠之间是相当的。与WT小鼠相比，p38 α(+/-)小鼠的血小板在体外和体内与肿瘤细胞的结合较差。经静脉注射肿瘤细胞后，E-和p -选择素mrna在肺内被显著诱导。然而，这些选择素mrna在p38 α(+/-)小鼠中的诱导作用比在WT小鼠中弱。此外，与WT小鼠相比，p38 α(+/-)小鼠肺内皮细胞中e -选择素和血小板中p -选择素的静息表达水平受到抑制。与WT小鼠相比，p38 α(+/-)小鼠肺内皮细胞上的肿瘤细胞数量明显减少。肿瘤细胞通过p38 α(+/-)小鼠肺内皮细胞的迁移活性与WT小鼠相似。这些结果表明p38 α在肿瘤细胞外渗中起重要作用，可能通过调节肿瘤血小板聚集物的形成及其与内皮细胞的相互作用参与了血液转移的一个步骤。
To study the role of p38 mitogen-activated protein kinase ( p38) activity during the process of metastasis, p38 alpha(+/-) mice were subjected to an in vivo metastasis assay. The number of lung colonies of tumor cells intravenously injected in p38 alpha(-/-) mice was markedly decreased compared with that in wild-type (WT) mice. On the other hand, the time-dependent increase in tumor volume after subcutaneous tumor cells transplantation was comparable between WT and p38 alpha(+/-) mice. Platelets of p38 alpha(+/-) mice were poorly bound to tumor cells in vitro and in vivo compared with those of WT mice. E- and P-selectin mRNAs were markedly induced in the lung after intravenous injection of tumor cells. However, the induction of these selectin mRNAs in p38 alpha(+/-) mice was weaker than that in WT mice. Furthermore, the resting expression levels of E-selectin in lung endothelial cells and P-selectin in platelets of p38 alpha(+/-) mice were suppressed compared with those of WT mice. The number of tumor cells attached on lung endothelial cells of p38 alpha(+/-) mice was significantly reduced compared with that of WT mice. The transmigrating activity of tumor cells through lung endothelial cells of p38 alpha(+/-) mice was similar to that of WT mice. These results suggest that p38 alpha plays an important role in extravasation of tumor cells, possibly through regulating the formation of tumor-platelet aggregates and their interaction with the endothelium involved in a step of hematogenous metastasis.