Role of the alpha v-integrin subunit in cell proliferation, apoptosis and tumor metastasis of laryngeal and hypopharyngeal squamous cell carcinomas: a clinical and in vitro investigation.
The objective of this study was to investigate the role of alpha v-integrin subunit (ITGAV, CD51) in invasion and metastasis of the laryngeal and hypopharyngeal squamous cell carcinomas and to evaluate whether an antisense oligonucleotide sequence (ASONs) targeting ITGAV gene can result in proliferative inhibition and induce to apoptosis of laryngeal carcinoma cell lines (Hep-2). Firstly, a tissue microarray contained 75 primary carcinomas, 29 non-cancerous normal tissues and 20 metastatic lymph nodes was constructed and used to detect the expression of ITGAV by immunohistochemistry. The changes of ITGAV expression from each group were assessed and correlated to the clinical parameters of the patients. Secondly, the ASONs targeting ITGAV gene was transfected into Hep-2 cells in vitro. The proliferative ability of the cells after transfection was measured by MTT assay and the apoptosis was detected using flow cytometry. Results showed that the expression of ITGAV was significantly correlated with differentiation and lymph node metastasis of these cancers. In vitro test showed that the proliferative ability of Hep-2 cells was significantly inhibited by ASONs in a way of concentration- and time-depending mode, and a significant apoptosis of Hep-2 cells was also observed after ASONs transfection. In conclusion, the expression of ITGAV was significantly correlated with differentiation and metastasis of the laryngeal and hypopharyngeal carcinomas; down-regulation of ITGAV gene could inhibit proliferation of Hep-2 cells and induce to its apoptosis. These results suggest that ITGAV gene may become a promising prognostic marker and new treatment target for these cancers.
Lu
Jian Guang
JG
Department of Otolaryngology/Head and Neck Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China.
Sun
Ya Nan
YN
Wang
Chao
C
Jin
De Jun
DJ
Liu
Ming
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D039302:Integrin alphaVbeta3 / Q000235:genetics* / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques
D014408:Biomarkers, Tumor; D039302:Integrin alphaVbeta3; D012333:RNA, Messenger