Background: Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces\nimmune responses. Our research has revealed that threonyl-tRNA synthetase (TARS) has an extracellular angiogenic\nactivity separate from its function in protein synthesis. The objective of this study was to test the hypothesis that\nTARS expression in clinical samples correlates with angiogenic markers and ovarian cancer progression.\nMethods: Protein and mRNA databases were explored to correlate TARS expression with ovarian cancer. Serial\nsections of paraffin embedded ovarian tissues from 70 patients diagnosed with epithelial ovarian cancer and 12\ncontrol patients were assessed for expression of TARS, vascular endothelial growth factor (VEGF) and PECAM using\nimmunohistochemistry. TARS secretion from SK-OV-3 human ovarian cancer cells was measured. Serum samples\nfrom 31 tissue-matched patients were analyzed by ELISA for TARS, CA-125, and tumor necrosis factor-? (TNF-?).\nResults: There was a strong association between the tumor expression of TARS and advancing stage of epithelial ovarian\ncancer (p < 0.001). TARS expression and localization were also correlated with VEGF (p < 0.001). A significant proportion of\nsamples included heavy TARS staining of infiltrating leukocytes which also correlated with stage (p = 0.017). TARS was\nsecreted by ovarian cancer cells, and patient serum TARS was related to tumor TARS and angiogenic markers, but did not\nachieve significance with respect to stage. Multivariate Cox proportional hazard models revealed a surprising inverse\nrelationship between TARS expression and mortality risk in late stage disease (p = 0.062).\nConclusions: TARS expression is increased in epithelial ovarian cancer and correlates with markers of angiogenic\nprogression. These findings and the association of TARS with disease survival provide clinical validation that TARS is\nassociated with angiogenesis in ovarian cancer. These results encourage further study of TARS as a regulator of the tumor\nmicroenvironment and possible target for diagnosis and/or treatment in ovarian cancer.
Loading....