Published online Jul 7, 2005. doi: 10.3748/wjg.v11.i25.3877
Revised: January 2, 2005
Accepted: January 5, 2005
Published online: July 7, 2005
AIM: Hepatocyte growth factor (HGF) is a multifunctional growth factor which has pleiotrophic biological effects on epithelial cells, such as proliferation, motogenesis, invas-iveness and morphogenesis. There are few reports about the role of HGF played in the colorectal cancer invasion. In the present study, we tried to investigate the possible mechanism of HGF involved in the invasion of colorectal cancer cells in vitro.
METHODS: Matrigel migration assay was used to analyze the migrational ability of Caco-2 and Colo320 in vitro. We detected the mRNA expressive levels of MMP-2, MMP-9 and their natural inhibitors TIMP-1, TIMP-2 in Caco-2 cells by reverse-transcription polymerase chain reaction (PCR) technique.
RESULTS: After 48 h incubation, there were notable differences when we compared the migrational numbers of Caco-2 cells in the group of HGF and PD98059 (the inhibitor of p42/p44MAPK) with the control (104.40 ± 4.77 vs 126.80 ± 5.40, t = 7.17, P = 0.002 < 0.01; 104.40 ± 4.77 vs 82.80 ± 4.15, t = 7.96, P = 0.001 < 0.01). The deviation between the HGF and PD98059 was significant (P < 0.01). Compared with controls, MMP-2 and MMP-9 mRNA expres-sions were up-regulated by HGF (0.997 ± 0.011 vs 1.207 ± 0.003, t = 35.002,P = 0.001 < 0.01; 0.387 ± 0.128 vs 0.971 ± 0.147, t = 106.036, P = 0.0000 < 0.01, respectively); compared with controls, TIMP-1, TIMP-2 mRNA expressions were increased by PD98059 (1.344 ± 0.007 vs 1.905 ± 0.049, t = 17.541, P = 0.003 < 0.01; 1.286 ± 0.020 vs 1.887 ± 0.022, t = 24.623, P = 0.002 < 0.01, respectively).
CONCLUSION: HGF promoted Caco-2 migration mainly by p42/p44MAPK pathway; HGF/SF stimulated the expression of MMP-2, MMP-9 in Caco-2 and enabled tumoral cells to damage the ECM and reach the distant organ and develop metastasis; HGF played the function of promoted-invasion and promoted-metastasis, in which cellular selection was possible.