Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells
published online 04 May 2009.
The gelatinases B (MMP9) and A (MMP2) are two members of the matrix metalloproteinase (MMPs) family that are expressed in human cancer, and play a critical role in tumor cell invasion and metastasis. Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the effect and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In this study, we investigated the expression of Cav1, MMP2, and MMP9 in several different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the mechanisms underlying these observations, we further investigated the expression of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene could inhibit pancreatic carcinoma cell invasion, at least in part, probably through Erk-MMP signal pathway, suggesting that the endogenous expression or re-expression of Cav1 might help therapeutically reduce their invasive potential in pancreatic carcinoma cells.
∗Department of Pathology, Shanghai Medical College of Fudan University, Shanghai, China
†Department of Pathology, Shanghai Medical School, Research Center for Pathology, Institute of Biomedical Science, Fudan University, Shanghai, China
‡Department of Pathology, Huashan Hospital of Fudan University, Shanghai, China
To whom correspondence and reprint requests should be addressed at Department of Pathology, Shanghai Medical College of Fudan University, 130 Dongan Road, Shanghai 200032, PR China.