The Mechanism Of Osteopontin In Pancreatic Cancer Invasion And Metastasis

Objective: To study the expression of Osteopontin (OPN), CD44v6, MMP-2 and VEGF in human pancreatic carcinomas, the expression of Osteopontin in islet cell tumors and analyze the relationship between their expression and clinicopathologic features; and to investigate the effect of OPN on the PANC-1 cells reproductive activity and the expression of VEGF, MMP-2 in PANC-1cells.Methods: OPN expression was detected in 8 cases of pancreatic carcinomas and corresponding surrounding tissues by RT-PCR. The expression of OPN, CD44v6, MMP-2 and VEGF was tested by immunohistochemistry in 43 cases of pancreatic carcinomas, 34 cases of pancreatic cancer surrounding tissues and 14 cases of islet cell tumors; PANC-1 cells were transfected with Osteopontin small interfering RNA (OPN-SiRNA) by lipofectmine 2000, and transfectants were confirmed using Western blot for OPN. The reproductive activity was detected by MTT, VEGF and MMP-2 expressions were detected by Western blot.Results: OPN mRNA expression was higher in 6 cases of pancreatic carcinomas than that in corresponding surrounding tissues. In 43 cases of pancreatic carcinomas, the expression rates of OPN, CD44v6, MMP-2 and VEGF were 65.1%, 62.7%, 60.5% and 53.5% respectively; in 34 cases of pancreatic cancer surrounding tissues, the expression rates of OPN, CD44v6, MMP-2 and VEGF were 20.6%, 20.6%, 23.5% and 14.7% respectively; in 14 cases of islet cell tumors the expression rates of OPN was 21.4%. OPN expression was higher in patients with lymph node metastases (P＜0.05); CD44v6 expression was higher in patients with lymph node metastases and histological gradeⅢ(P＜0.05); the expression of MMP-2 was higher only in patients with histological gradeⅢ(P＜0.05); VEGF expression was higher in patients not only with lymph node metastases and histological gradeⅢ, but also with tumor size (＞3cm)(P＜0.05). And there are strong relationship between CD44v6, MMP-2, VEGF and OPN (rc=0.446, rm=0.406, rv=0.393) (P＜0.05). PANC-1 cells were successfully transfected with OPN-SiRNA, and the OPN expression was down-regulated by Western blot, and there was no significant change in reproductive activity. Using Western blot, we found OPN can regulate MMP-2 expression but not VEGF. Transfection of OPN-SiRNA decreased MMP-2 expression.Conclusion: OPN, CD44v6, MMP-2 and VEGF express higher in pancreatic carcinomas. They may play an important role in the progression of human pancreatic carcinomas and they may involve in the invasion and metastasis of pancreatic carcinomas. OPN may promote pancreatic cancer invasion and metastasis by enhancing MMP-2 expression not VEGF or cell proliferation.