P -选择素对黑色素瘤细胞整合素β1表达的影响(1)
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[摘要] 目的:研究P-选择素对黑色素瘤细胞整合素β1表达的影响,探讨P-选择素在肿瘤转移中的作用。方法:培养黑色素瘤细胞B16F10,在加或不加p38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580的情况下,用P-选择素蛋白进行刺激,用蛋白质印迹(Western Blot)检测刺激后B16F10细胞整合素β1蛋白表达及p38 MAPK信号分子磷酸化水平的改变,用MTT法检测黏附细胞数目的变化。结果:P-选择素刺激B16F10细胞导致p38 MAPK磷酸化水平增高,整合素β1表达上调,用特异性阻断剂阻断p38 MAPK活化可以抑制P-选择素的诱导作用。MTT检测结果显示P-选择素刺激可增加细胞与整合素β1配基纤维粘连蛋白的黏附能力,说明细胞整合素β1表达增高。结论:P-选择素可以通过激活p38 MAPK途径诱导黑色素瘤B16F10细胞整合素β1的表达,提高肿瘤细胞的黏附能力,这可能是其促进肿瘤转移的机制之一。
[关键词] P-选择素;整合素β1;p38丝裂原活化蛋白激酶;肿瘤
[中图分类号] R730.23 [文献标识码]A [文章编号]1674-4721(2010)06(c)-013-03
Effects of P-selectin on the expression of β1 integrin in melanoma cells
LI Ming1, CHEN Weiqiang1, LI Yan2, LUO Shaohong1, WANG Weizhang1
(1. School of Basic Courses, Guangdong Pharmaceutical College, GuangdongProvince, Guangzhou510006, China;2. School of Basic Medical Science, Guangzhou University of Chinese Medicine, GuangdongProvince,Guangzhou510006, China)
[Abstract] Objective: To investigate the effects of P-selectin on the expression of integrin β1 and the phosphorylation of p38 MAPK in melanoma cell line B16F10. Methods: B16F10 cells were treated with P-selectin in the presence or absence of SB203580, an inhibitor of p38 MAPK. The protein expression of integrin β1 and the phosphorylation level of p38 MAPK were determined by Western Blot. Cell adhesion was detected by MTT assay. Results: P-selectin significantly enhanced the expression of integrin β1 in B16F10 cells and the phosphorylation level of p38 MAPK. Inhibit p38 MAPK by SB203580 suppressed P-selectin-induced integrin β1 expression. Treated with P-selectin also enhanced the adhesion of B16F10 cells to fibronectin. Conclusion: P-selectin might effectively up-regulated integrin β1 expression in melanoma cells via p38 MAPK pathway, which may contribute, in part at least, to the tumor metastasis.
[Key words] P-selectin; Integrin β1; p38 MAPK; Tumor
转移是肿瘤患者死亡的主要原因,寻找和研究与肿瘤转移密切相关的分子是防治肿瘤转移的关键[1]。肿瘤转移包括肿瘤细胞脱离原发部位、穿透毛细血管、在血液中的运输、黏附并跨血管壁转运到靶组织形成继发瘤等过程,其中肿瘤细胞与血管内皮细胞及细胞外基质的黏附是肿瘤从血液到组织的关键[2]。选择素和整合素是重要的黏附分子,分别介导了白细胞的边集、黏附和游出。研究证实,肿瘤细胞游出血管的过程与白细胞类似,也是由黏附分子所介导的[3] ......
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