Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. Previously, we identified the angiostatic agent tryptophanyl-tRNA synthetase (TrpRS) as a dysregulated protein in OSCC based on a proteomics approach. Herein, we show that TrpRS is overexpressed in OSCC tissues (139/146, 95.2%) compared with adjacent normal tissues and that TrpRS expression positively correlates with tumor stage, overall TNM stage, perineural invasion and tumor depth. Importantly, the TrpRS levels were significantly higher in tumor cells from metastatic lymph nodes than in corresponding primary tumor cells. TrpRS knockdown or treatment with conditioned media obtained from TrpRS-knockdown cells significantly reduced oral cancer cell viability and invasiveness. TrpRS overexpression promoted cell migration and invasion. In addition, the extracellular addition of TrpRS rescued the invasion ability of TrpRS-knockdown cells. Subcellular fractionation and immunofluorescence staining further revealed that TrpRS was distributed on the cell surface, suggesting that secreted TrpRS promotes OSCC progression via an extrinsic pathway. Collectively, our results demonstrated the clinical significance and a novel role of TrpRS in OSCC.
Highlights
Oral cancer is one of the most common neoplasms of the head and neck, accounting for 263, 900 newly diagnosed cases and 128, 000 deaths worldwide in 2008 [1]
The expression levels of STAT1 and MX1 were up-regulated in Oral squamous cell carcinoma (OSCC) tumors (7/9 and 9/9 for STAT1 and MX1, respectively), whereas the levels of ANXA2 were similar between the tumor tissues and the adjacent normal tissues
To examine whether the mRNA level of TrpRS is dysregulated in OSCC, we analyzed the gene expression levels of TrpRS in oral cancer tissues compared with normal tissues based on the Oncomine 4.5 database
Summary
Oral cancer is one of the most common neoplasms of the head and neck, accounting for 263, 900 newly diagnosed cases and 128, 000 deaths worldwide in 2008 [1]. In Taiwan, the most prevalent area of oral squamous cell carcinoma (OSCC) occurrence worldwide, the incidence rate (increased by 5.82- and 2.35-fold in males and females, respectively) and mortality rate (increased by 2.26-fold) have significantly increased in recent decades [2]. Despite major advances in therapy, the 5-year survival rate of OSCC patients remains less than 50%. The metastatic processes of OSCC are dependent on the vasculature, nerves or lymphatic vessels adjacent to regional or distal metastases [6, 7], and the extent of OSCC metastasis reflects the efficiency of therapy [8]. It is worthwhile to search for tumor markers and to understand their roles in OSCC progression to stratify patients according to their risk of metastasis
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