Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and migration on extracellular matrix
Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and migration on extracellular matrix
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DOI：
10.1016/s0168-8278(00)00090-8
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发表时间：
2001-03-01
影响因子：
25.7
通讯作者：
López-Cabrera, M
中科院分区：
文献类型：
--
作者：
Lara-Pezzi, E;Majano, PL;López-Cabrera, M
背景/目标：B型肝炎病毒HBx蛋白与肝细胞癌（HCC）的发生、发展有关，但其在肿瘤扩散中的作用尚不清楚。肿瘤细胞通过细胞外基质（ECM）的迁移是肿瘤转移的关键步骤。我们的目的是研究HBx对整合素介导的细胞-ECM相互作用的影响，以及其对细胞迁移的可能影响。通过静态粘附实验评价细胞-ECM相互作用，使用阻断和刺激抗β 1整联蛋白mAb，通过流式细胞术分析ECM受体表达，通过免疫荧光分析确定活化的pi整联蛋白亚基的细胞分布，并且通过伤口愈合测定确定细胞运动性。携带HBx的细胞显示出对纤连蛋白的粘附降低，这与α 5整合素亚基表达的降低相关。活化的β 1亚基重新分布到携带HBx的细胞的伪足突起的尖端，而在对照细胞中则均匀分布。HBx诱导的细胞迁移被废除不可逆的刺激Pt integrin.Conclusions：这些结果表明，HBx可能发挥作用，在肿瘤扩散的调节粘附-脱粘附平衡的细胞在原发肿瘤部位，有利于整合素介导的细胞迁移。(C)2001年欧洲肝脏研究协会，由Elsevier Science B，V出版，保留所有权利。
Background/Aims: The hepatitis B virus HBx protein is associated with the development of hepatocellular carcinoma (BCC), However, its possible contribution to tumor spreading has not been explored. The migration of tumor cells through the extracellular matrix (ECM) represents a crucial step in tumor metastasis, Our aim was to study the effect of HBx on the integrin-mediated cell-ECM interaction, and its possible consequences for cell migration.Methods: Cell-ECM interaction was evaluated by static adhesion experiments, using blocking and stimulating anti-beta1 integrin mAbs, ECM receptor expression was analyzed by flow cytometry, The cellular distribution of the activated pi integrin subunit was determined by immunofluorescence analysis, and cell motility was determined by wound-healing assays.Results: HBx-bearing cells showed decreased adhesion to fibronectin, which correlated with a decreased expression of the alpha5 integrin subunit, The activated pi subunit was redistributed to the tips of pseudopodial protrusions of HBx-bearing cells, whereas it was evenly localized in the control cells. HBx-induced cell migration was abrogated by irreversible stimulation of Pt integrins.Conclusions: These results suggest that HBx might play a role in tumor spreading by modulating the adhesion-deadhesion balance of the cells in the primary tumor site and favoring integrin-mediated cell migration.(C) 2001 European Association for the Study of the Liver, Published by Elsevier Science B,V, All rights reserved.