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FLNA suppresses nasopharyngeal carcinoma cell proliferation and migration partially through an MMP-9-dependent mechanism
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Abstract:
Objective: This study aimed to determine the expression of filamin A (FLNA) in nasopharyngeal carcinoma and evaluate the effect of FLNA overexpression on nasopharyngeal cancer cell proliferation and migration in vitro . Methods: Fresh nasopharyngeal cancer (NPC, n =63) and non-cancer nasopharyngeal tissue surrounding but at least 2 cm from the tumor proper ( n =21) specimens were collected from NPC patients who were treat in the Department of Pathology in Tangshan Municipal People’s Hospital between January, 2008 and December, 2008. The presence and quantity of FLNA protein in these specimens was assessed by immunohistochemistry and Western blotting analysis. To evaluate the effect of FLNA on NPC cell proliferation and migration in vitro and elucidate the possible underlying mechanisms, nasopharyngeal cancer CNE2 cells were infected with a lentiviral vector carrying the human FLNA gene (pLenti6-FLNA) or a control lentiviral vector and the cell viability, migration capacity and MMP-9 protein content of the vector-infected cells were assessed by MTT assay, Transwell assay and Western blotting analysis respectively. Result: FLNA protein was detected positive in 35.6% (23/63) of nasopharyngeal carcinoma specimens and 66.7% (14/21) of non-carcinoma specimens ( P <0.05). The relative amount of FLNA protein in nasopharyngeal cancer tissue was significantly lower than in normal nasopharyngeal tissue ( P <0.05). The level of FLNA protein was correlated with T stages, lymph node metastasis, clinic stage and histological grade ( P <0.05). Overexpression of FLNA resulted in significant decreases in proliferation, migration and invasion, and MMP-9 protein content CNE2 cells in vitro ( P <0.05). Conclusion: FLNA may be a negative regulator to nasopharyngeal cancer growth and invasion. This negative effect of FLNA is mediated, at least partially, by an MMP-9-dependent mechanism.
Keywords:
filamin A(FLNA) ; nasopharyngeal carcinoma ; gene transfection ; tumor metastasis ; MMP-2
