Effects of hepatocyte growth factor/scatter factor on the invasion of colorectal cancer cells in vitro.
OBJECTIVE
Hepatocyte growth factor (HGF) is a multifunctional growth factor which has pleiotrophic biological effects on epithelial cells, such as proliferation, motogenesis, invasiveness 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 expressions 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).


CONCLUSIONS
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.
Li
Hong-Wu
HW
Department of Oncology, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China. lhw-005@163.com
Shan
Ji-Xian
JX
D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000503:physiopathology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology
D017228:Hepatocyte Growth Factor