Lara-Pezzi E, Majano P L, Yáñez-Mó M, Gómez-Gonzalo M, Carretero M, Moreno-Otero R, Sánchez-Madrid F, López-Cabrera M
Unidad de Biología Molecular, Hospital Universitario de la Princesa, Madrid, Spain.
J Hepatol. 2001 Mar;34(3):409-15. doi: 10.1016/s0168-8278(00)00090-8.
BACKGROUND/AIMS: The hepatitis B virus HBx protein is associated with the development of hepatocellular carcinoma (HCC). 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.
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 beta1 integrin subunit was determined by immunofluorescence analysis, and cell motility was determined by wound-healing assays.
HBx-bearing cells showed decreased adhesion to fibronectin, which correlated with a decreased expression of the alpha5 integrin subunit. The activated beta1 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 beta1 integrins.
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.
背景/目的：乙型肝炎病毒X蛋白（HBx）与肝细胞癌（HCC）的发生发展相关。然而，其对肿瘤扩散的潜在作用尚未得到研究。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与ECM相互作用的影响及其对细胞迁移的可能影响。
通过静态黏附实验评估细胞与ECM的相互作用，使用阻断和刺激抗β1整合素单克隆抗体。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β1整合素亚基的细胞分布，并通过伤口愈合试验确定细胞运动性。
携带HBx的细胞对纤连蛋白的黏附减少，这与α5整合素亚基表达降低相关。活化的β1亚基重新分布到携带HBx的细胞伪足突起的尖端，而在对照细胞中其分布均匀。β1整合素的不可逆刺激消除了HBx诱导的细胞迁移。
这些结果表明，HBx可能通过调节原发性肿瘤部位细胞的黏附-去黏附平衡并促进整合素介导的细胞迁移，在肿瘤扩散中发挥作用。
