Expression of MMP-2, HIF-1alpha and VEGF in Colon Adenoma and Colon Cancer / 대한소화기학회지

ABSTRACT

BACKGROUND/AIMS: This study was aimed to investigate the expression of matrix metalloproteinase-2 (MMP-2), hypoxia-inducible factor (HIF)-1alpha, and vascular endothelial growth factor (VEGF) in colonic adenoma-carcinoma sequence. METHODS: Thirty-two tissue samples of colon adenoma, 11 of early colon cancer and 36 of advanced colon cancer were collected by colonoscopic biopsy. Normal colonic tissues were also collected from the same subjects. The mRNA expression levels of MMP-2, HIF-1alpha, and VEGF were quantitated using semiquantitative reverse transcription polymerase chain reactions. The protein expressions of activated MMP-2 and HIF-1alpha were examined by gelatin zymography and by Western blot in surgically resected cases, respectively. RESULTS: The expression level of MMP-2 mRNA showed a progressive increase in the advance of the colorectal adenoma-carcinoma sequence (p<0.05). In colon cancer tissues, the expression level of MMP-2 mRNA showed an increasing trend according to differentiation, lymphatic invasion and Dukes' stage (p<0.05). The protein expression of activated MMP-2 was observed in 10 of 11 (91%) cases of cancer tissues. The mRNA expression levels of HIF-1alpha and VEGF were greater in tissues of early and advanced colon cancer compared with colon adenoma (p<0.05; p<0.001). The protein expression of HIF-1alpha was observed in 9 of 11 (82%) cases of cancer tissues. The mRNA expression level of HIF-1alpha showed a positive correlation with MMP-2 and VEGF, respectively (r=0.52, p<0.001; r=0.76, p<0.001). CONCLUSIONS: MMP-2, HIF-1alpha, and VEGF may be useful in detecting early carcinogenesis and progression of colon cancer.