Fei Han1, Jie Zhang1, Jinchen Shao1, Xianghua Yi2. 1. Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai, 389 Xincun Road, Shanghai, China. 2. Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai, 389 Xincun Road, Shanghai, China. Electronic address: yixhxf@163.com.
Abstract
PURPOSE: This study investigated the relationships of caveolin-1 expression with clinical pathologic parameters and the prognosis of patients with large cell lung carcinoma. This study also explored the roles of caveolin-1 in cell invasiveness, matrix metalloproteinase (MMP) expression, and non-small cell lung carcinoma activity in vitro. METHODS: A total of 120 tissue samples were immunohistochemically analyzed for caveolin-1 expression. Cell invasion ability was measured by a Transwell invasion assay. Protein expression was assessed by Western blotting. MMP activity was detected by gelatin zymography. RESULTS: Caveolin-1 was expressed in 54 of 120 (45.0%) cases of large cell lung carcinoma. Caveolin-1 expression was significantly correlated with node status (N0 vs. N1, N2, and N3; P=0.005) and advanced pTNM stage (Stages I and II vs. Stage III, P<0.001). Patients with caveolin-1-positive expression had a poorer prognosis than did those with caveolin-1-negative expression (P<0.001). The knockdown of caveolin-1 in H460 and 95D cells reduced the invasive ability of the cells and the expression of phosphorylated epidermal growth factor receptor (EGFR), phospho-extracellular signal-regulated kinases 1 and 2, MMP2, and MMP9; the protein level and activity of MMP2 and MMP9 were also decreased by the inhibition of EGFR activity in H460 and 95D cells. CONCLUSIONS: The expression of caveolin-1 was positively correlated with an advanced pathologic stage. Thus, caveolin-1 could act as a predictor of a poor prognosis in patients with large cell lung carcinoma. In addition, the downregulation of caveolin-1 reduced both the invasive ability of tumor cells and the protein and activity levels of MMP2 and MMP9 in vitro, suggesting the involvement of EGFR/MMP signaling in this process.
PURPOSE: This study investigated the relationships of caveolin-1 expression with clinical pathologic parameters and the prognosis of patients with large cell lung carcinoma. This study also explored the roles of caveolin-1 in cell invasiveness, matrix metalloproteinase (MMP) expression, and non-small cell lung carcinoma activity in vitro. METHODS: A total of 120 tissue samples were immunohistochemically analyzed for caveolin-1 expression. Cell invasion ability was measured by a Transwell invasion assay. Protein expression was assessed by Western blotting. MMP activity was detected by gelatin zymography. RESULTS:Caveolin-1 was expressed in 54 of 120 (45.0%) cases of large cell lung carcinoma. Caveolin-1 expression was significantly correlated with node status (N0 vs. N1, N2, and N3; P=0.005) and advanced pTNM stage (Stages I and II vs. Stage III, P<0.001). Patients with caveolin-1-positive expression had a poorer prognosis than did those with caveolin-1-negative expression (P<0.001). The knockdown of caveolin-1 in H460 and 95D cells reduced the invasive ability of the cells and the expression of phosphorylated epidermal growth factor receptor (EGFR), phospho-extracellular signal-regulated kinases 1 and 2, MMP2, and MMP9; the protein level and activity of MMP2 and MMP9 were also decreased by the inhibition of EGFR activity in H460 and 95D cells. CONCLUSIONS: The expression of caveolin-1 was positively correlated with an advanced pathologic stage. Thus, caveolin-1 could act as a predictor of a poor prognosis in patients with large cell lung carcinoma. In addition, the downregulation of caveolin-1 reduced both the invasive ability of tumor cells and the protein and activity levels of MMP2 and MMP9 in vitro, suggesting the involvement of EGFR/MMP signaling in this process.