Metastasis Of Pancreatic Cancer Invasion

Pancreatic ductal ademocarcinoma is the eighth leading cause of cancer mortality in China and the fourth in United States. The incidence of Pancreatic ductal ademocarcinoma is increasing. So far neither an early diagnosis nor a therapeutic strategy for advanced lesions has been developed yet. The death to incidence ratio of pancreatic ductal carcinoma is approximate to 0.98-0.993. The overall 5-year survival rate of pancreatic carcinoma is less than 5%, which is largely due to the difficulty in early diagnosis. More than 85% of patients have the disease extending beyond the pancreas at the time of diagnosis, rendering surgical and medical intervention ineffective. For the 15-20% of patients who undergo potentially curative resection, the 5-year survival is only 20%. It is an urgent mission for both the clinicians and the scientists who devote themselves to pancreatic cancer to find a breakthrough using new techniques.Ezrin is a member of the ERM family, it provides a functional link between the plasma membrane and the cortical actin cytoskeleton of the cell, and participates in crucial signal transduction pathways. There are increasing evidences that it can regulate tumor progression and metastasis. However, the role of ezrin in pancreatic cancer has not clearly delineated.Ezrin expression leval was interrupted in pancreatic cancer cells MiaPaCa-2 by ezrin knock-down and overexpression, and the biological behavior changes in these cells were observed and analyzed.1. Knock-down ezrin expression in pancreatic cancer cells MiaPaca-2 by RNAi: The suppression of ezrin did not influence cells proliferation and the cell cycle in vitro; but ezrin depression can inhibit the formation of cell protrusion and cell microvilli as well as cause a decrease in cell motility and invasiveness. Furthermore, we revealed that ezrin silencing can reduce the anchorage-independent growth of the tumor cells in soft agar.2. Ezrin overexpression in pancreatic cancer cells MiaPaca-2: The overexpression of ezrin did not influence cells proliferation and the cell cycle in vitro; but it can enhance the formation of cell protrusion and cell microvilli as well as cause an increase in cell motility and invasiveness. Furthermore, we revealed that ezrin overexpression can raise the ability of the anchorage-independent growth of the tumor cells in soft agar.3. Gelatin zymography assay revealed that overexpression of ezrin can induce the expression of MMP-9, but the effect of ezrin knock-down on the expression of gelatinase is not obvious. Ezrin overexpression can also induce the activation of Erkl/2, but ezrin silencing can not influence the activation of Erkl/2. The alteration of ezrin expression could not influence the Akt activation, total Akt as well as total Erkl/2 protein level. There may be another pathway involved in ezrin induced pancreatic ductal adenocarcinoma cells motiliy and invasiness.Our experiments showed that the alteration of ezrin expression can induce the changes in cell protrusion and cell microvilli, cell motility, invasiveness as well as the ability of the anchorage-independent growth of the tumor cells. The inactivation of Erkl/2 may induce the actin cytoskeleton reappearance and contribute to alteration of cell motility and invasiveness ability. The latter may be related to induced MMP-9 expression when ezrin was overexpressed.Consistent with these results, ezrin may be an important target for inhibiting the invasion and metastasis of pancreatic ductal adenocarcinoma.