The interaction of HAb18G/CD147 with integrin α6β1 and its implications for the invasion potential of human hepatoma cells
- Equal contributors
1 Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR China
2 Department of Hepatobiliary Surgery, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR China
3 Department of Clinical Immunology, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR China
4 Department of Emergency Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA, 19107, USA
5 Department of Cardiology, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR China
BMC Cancer 2009, 9:337 doi:10.1186/1471-2407-9-337Published: 23 September 2009
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 α3β1. However, it has never been investigated whether α3β1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells.
Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin α6β1 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 α6β1. Invasion potential was evaluated with an invasion assay and gelatin zymography.
We found that integrin α6β1 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 α6β1 antibodies (P < 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P < 0.05). Importantly, no additive effect between Wortmannin and α6β1 antibodies was observed, indicating that α6β1 and PI3K transmit the signal in an upstream-downstream relationship.
These results suggest that α6β1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.