Metalloproteinase 2 and 9 activity in the development of pancreatic cancer

Pancreatic adenocarcinoma is the fourth most common cancer occurring in both women and men. In Poland, within the past ten years the number of deaths from pancreatic cancer increased by 29%.The aim of the study was to determine the correlation between the activity of metalloproteinase (MMP) 2 and 9 and progression and aggressiveness of pancreatic cancer.

Tissue samples were collected from 36 patients with diagnosed pancreatic adenocarcinoma who underwent Whipple resection. Tumor tissues were analyzed by gel zymography, zymography in situ and immunohistochemistry.

The activity of MMPs was found mainly in cancer cells. Active form of MMP2 (62 kDa) was present in 88% of cases and MMP9 (83 kDa) in 38% of cases. By contrast, immunohistochemical staining revealed the presence of metalloproteinase 9 in all studied tissues. MMP activity was assessed against histological grade of the tumor. In the case of group G1 there was no activity of matrix metalloproteinase 9. By comparing the activity we concluded that the activity of MMPs in tumors with the highest degree of differentiation is significantly lower than in G2 and G3. Metalloproteinase 9 expression analysis revealed no significant differences between the groups of various degrees of histological maturity. The level of expression did not differ between the groups N0 and N1.

Lack of metalloproteinase 9 activity in group G1 may indicate that MMP9 is activated only in higher tumor grades. We have shown that an active form of MMP2 is found in all histological grades, which supports its involvement in the development of pancreatic cancer. Metalloproteinases are attractive target of anticancer therapy but not only the level of expression of metalloproteinases should be taken into account but also their level of activity and factors associated with their activation.