The interaction of HAb18G/CD147 with integrin [alpha]6[beta]1 and its implications for the invasion potential of human hepatoma cells

• Published in: BMC cancer 2009-09, Vol.9, p.337
• Main Authors: Dai, Jing-yao, Dou, Ke-feng, Wang, Cong-hua, Zhao, Pu, Lau, Wayne Bond, Tao, Ling, Wu, Ya-mei, Tang, Juan, Jiang, Jian-li, Chen, Zhi-nan
• Format: Article
• Language: English
• Subjects: Development and progression; Emergency medical care; Genetic aspects; Glycoproteins; Hepatoma; HIV; Human immunodeficiency virus; Kinases; Neural networks; Phosphorylation; Physiological aspects; Protein kinases; Proteins; Risk factors; Studies
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-9-337

Background HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin [alpha]3[beta]1. However, it has never been investigated whether [alpha]3[beta]1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. Methods Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin [alpha]6[beta]1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin [alpha]6[beta]1. Invasion potential was evaluated with an invasion assay and gelatin zymography. Results We found that integrin [alpha]6[beta]1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin [alpha]6[beta]1 antibodies (P [less than] 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca.sup.2+ .sup.mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P [less than] 0.05). Importantly, no additive effect between Wortmannin and [alpha]6[beta]1 antibodies was observed, indicating that [alpha]6[beta]1 and PI3K transmit the signal in an upstream-downstream relationship. Conclusion These results suggest that [alpha]6[beta]1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.