Human beta-defensin-1 suppresses tumor migration and invasion and is an independent predictor for survival of oral squamous cell carcinoma patients

人类 β-防御素-1 抑制肿瘤迁移和侵袭,是口腔鳞状细胞癌患者生存的独立预测因子

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作者:Qi Han, Ruinan Wang, Chongkui Sun, Xin Jin, Dongjuan Liu, Xin Zhao, Lili Wang, Ning Ji, Jing Li, Yu Zhou, Ling Ye, Xinhua Liang, Lu Jiang, Ga Liao, Hongxia Dan, Xin Zeng, Qianming Chen

Background

Human beta-defensin-1 (hBD-1) has recently been considered as a candidate tumor suppressor in renal and prostate cancer. The

Conclusions

Overall, these data indicated that hBD-1 suppressed tumor migration and invasion of OSCC and was likely to be a prognostic biomarker and a potential target for treatment of OSCC.

Methods

HBD-1 expression in tissues at different stages of oral carcinogenesis, as well as OSCC cell lines was examined. HBD-1 was overexpressed in HSC-3, UM1, SCC-9 and SCC-25 cells and subjected to cell growth, apoptosis, migration and invasion assays. Tissue microarray constructed with tissues from 175 patients was used to examine clinicopathological significance of hBD-1 expression in OSCC.

Results

HBD-1 expression decreased from oral precancerous lesions to OSCC and was lower in OSCC with lymph node metastasis than those without metastasis. In vitro, the expression of hBD-1 was related to the invasive potential of OSCC cell lines. Induction of exogenous expression of hBD-1 inhibited migration and invasion of OSCC cells, probably by regulation of RhoA, RhoC and MMP-2; but had no significant effect on proliferation or apoptosis. In a cohort of patients with primary OSCC, cases with no expression of hBD-1 had more chance to be involved in lymph node metastasis. Eventually, the positive expression of hBD-1 was associated with longer survival of patients with OSCC, and multivariate analysis and ROC curve analysis confirmed hBD-1 positivity to be an independent prognostic factor of OSCC, especially OSCC at early stage. Conclusions: Overall, these data indicated that hBD-1 suppressed tumor migration and invasion of OSCC and was likely to be a prognostic biomarker and a potential target for treatment of OSCC.

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