Serum matrix metalloproteinase -2, -7 and -9 in the normal mucosa-adenoma-colorectal carcinoma sequence

Background: Matrix metalloproteinases (MMP-s) play a part in colorectal cancer (CRC) invasion and metastasis. Strong expression of many MMPs has been related to poor survival in CRC patients. However, the behavior of serum MMPs has scarcely been investigated in the normal mucosa-adenoma-adenocarcinoma sequence of the colon.

Methods: The MMP-2, MMP-7 and MMP-9 serum levels were determined in 14 patients with CRC, 8 patients with colorectal tubulovillous adenoma and low-grade dysplasia, 10 patients with inflammatory bowel disease (IBD) and 8 tumor-free control patients by ELISA technique. Statistical analysis with one-way ANOVA was performed. P value of <0.05 was considered significant.

Results: MMP-2 and MMP-9 serum antigen levels (mean values +/- standard deviation, ng/ml) were significantly higher in CRC and adenomas compared to controls (MMP-2: 176.8+/-35.2, 185.1+/-31.9 and 147.1+/-21.2, respectively, P<0.05; MMP-9: 645.9+/-149.8, 667.39+/-91.8 and 451.1+/-67.6, respectively, P<0.01). MMP-9 was also higher in patients with IBD compared to controls (637.1+/-154.6 vs. 451.1+/-67.6, P<0.05). Significantly higher MMP-7 levels were observed in patients with CRC and adenomas compared with IBD and controls (5.3+/-2.0, 5.2+/-1.8, 3.6+/-2.5 and 2.5+/-0.8, respectively, P<0.05).

Conclusions: We demonstrate that antigen levels of MMP-2, –7 and –9 were significantly higher in blood samples from patients with CRC and adenomas compared to the controls, suggesting that MMPs may have a crucial role not only in the invasive process of cancer, but also in the progression of colorectal premalignant adenomas into CRC. Our results confirm previous results obtained in colorectal tissues that MMP-9 could also contribute to the inflammatory processes in IBD.