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[Mechanism of enhanced invasiveness of human hepatocellular carcinoma by integrin alpha 6 beta 1].

OBJECTIVE
To study the mechanism of enhanced invasiveness of human hepatocellular carcinoma (HCC) by laminin (LN) receptor integrin alpha 6 beta 1.


METHODS
A stable transfectant of HCC Bel 7402 cell line, the alpha 6 beta 1 receptors of which were replaced by non-functional LN receptor alpha 6 beta 4-TR using dominant negative strategy, was used. Motility of the non-transfected, mock transfected and transfected tumor cells was assessed by the number of cells migrated to an area scratched out of cells on tumor cell monolayer. Tumor cell invasion was examined by cell penetration through a Matrigel layer in Boyden chamber. Matrix metalloproteinases (MMPs) secretion was detected by gelatin zymography.


RESULTS
The migration of HCC Bel 7402 cells expressing dominant negative alpha 6 beta 1 was significantly decreased. Their invasive capability was decreased by 46.7%. The secretion of MMP-9 was almost totally inhibited and the activated MMP-2 was decreased by 43.9%.


CONCLUSION
The decrease in cell motility, invasiveness and MMPs secretion of HCC cells expressing dominant negative alpha 6 beta 4 TR implies that LN-integrin interaction plays important role in HCC progression.