Caveolin-1 promotes an invasive phenotype and predicts poor prognosis in large cell lung carcinoma.
OBJECTIVE
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.
Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai, 389 Xincun Road, Shanghai, China.
Fei
F
Han
Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai, 389 Xincun Road, Shanghai, China.
Jie
J
Zhang
Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai, 389 Xincun Road, Shanghai, China.
Jinchen
J
Shao
Department of Pathology, Shanghai Tongji Hospital Affiliated to Shanghai Tongji University Shanghai, 389 Xincun Road, Shanghai, China. Electronic address: yixhxf@163.com.
Xianghua
X
Yi
D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051242:Caveolin 1 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate
D051242:Caveolin 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Caveolin-1; EGFR; Large cell lung carcinoma; MMP2; MMP9