Chemokine CCL3 facilitates the migration of hepatoma cells by changing the concentration intracellular Ca

Hepatol Res. 2010 Apr;40(4):424-31. doi: 10.1111/j.1872-034X.2009.00619.x. Epub 2010 Mar 4.

Abstract

Aim: Recurrence and metastasis are the major factors associated with the poor prognosis of hepatocellular carcinoma (HCC). It was confirmed that multiple chemokines and their receptors are related to the progression and metastasis of HCC. The aim of this research was to conduct an investigation into whether macrophage inflammatory protein-1alpha/CCL3, and its receptor CCR1 play a role in HCC invasion and metastasis.

Methods: We used reverse transcription polymerase chain reaction, immunocytochemistry and flow cytometry to detect CCR1 mRNA and protein expression in the four hepatoma cell lines HepG2, Hep3B, HLE and HLF; and we conducted a microscope cell migration experiment to observe the pseudopodia formation and mobility of the hepatoma cells. The concentration of intracellular calcium was measured by fluorescence microscopy.

Results: CCR1 mRNA and protein were positively expressed in the four hepatoma cell lines HepG2, Hep3B, HLE and HLF. Following CCL3 stimulation, obvious pseudopodia formation of hepatoma cells was observed using a fluorescence microscope. The cell migration experiment showed that after incubation with CCL3, the number of Hep3B cells which passed through the polycarbonate microporous filter membranes increased to an obvious extent. After CCL3 incubation, the intracellular Ca(2+) level of the Hep3B cells increased to an obvious extent.

Conclusion: Chemokine CCL3 facilitates the migration of hepatoma by changing the concentration intracellular Ca(2+). The CCL3-CCR1 axis may play an important role in HCC invasion and metastasis. It may also be a potential target for HCC therapy or for prevention of the recurrence and metastasis of HCC.