Exocyst complex component Sec8: a presumed component in the progression of human oral squamous-cell carcinoma by secretion of matrix metalloproteinases

• DOI: 10.1007/s00432-012-1356-2
• Publication Date: 2012-12-03T20:48:25Z
• Authors: Ayumi Yamamoto; Atsushi Kasamatsu; Shunsaku Ishige; Kazuyuki Koike; Kengo Saito; Yukinao Kouzu; Hirofumi Koike; Yosuke Sakamoto; Katsunori Ogawara; Masashi Shiiba; Hideki Tanzawa; Katsuhiro Uzawa
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; 0303 health sciences; Blotting, Western; Mouth Mucosa; Apoptosis; Middle Aged; Immunoenzyme Techniques; 03 medical and health sciences; Matrix Metalloproteinase 9; Cell Movement; Lymphatic Metastasis; Carcinoma, Squamous Cell; Cell Adhesion; Disease Progression; Humans; Matrix Metalloproteinase 2; Female; Mouth Neoplasms; Aged; Cell Proliferation

Sec8, a component of the exocyst complex, has been implicated in tethering of secretory vesicles to specific regions on the plasma membrane. To investigate the involvement of Sec8 in oral squamous-cell carcinoma (OSCC), we evaluated the expression status and effect of Sec8 in OSCC cell lines.Sec8 mRNA and protein expressions in human OSCC cell lines were assessed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting. Functional analyses, proliferation assay, invasiveness assay, and gelatin zymography in Sec8 knockdown cells were performed. Also the correlation between Sec8 expression and the clinicopathological features in 98 primary OSCCs samples was evaluated by immunohistochemistry.Sec8 mRNA and protein expression were significantly up-regulated in all cell lines (p < 0.05). Sec8 knockdown cells were characterized by reduced cellular proliferation, invasiveness, and secretion of matrix metalloproteinases (MMPs) (MMP-2, proMMP-2, and proMMP-9). Sec8 protein expression in primary OSCCs also was significantly (p < 0.05) greater than in normal counterparts, and higher Sec8 expression was correlated with tumor size (p = 0.03).Our results suggested for the first time that Sec8 might play a specific role in OSCC progression by mediating MMP secretion.