Abstract | BACKGROUND: Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces immune responses. Our research has revealed that threonyl-tRNA synthetase ( TARS) has an extracellular angiogenic activity separate from its function in protein synthesis. The objective of this study was to test the hypothesis that TARS expression in clinical samples correlates with angiogenic markers and ovarian cancer progression. METHODS: RESULTS: There was a strong association between the tumor expression of TARS and advancing stage of epithelial ovarian cancer (p < 0.001). TARS expression and localization were also correlated with VEGF (p < 0.001). A significant proportion of samples included heavy TARS staining of infiltrating leukocytes which also correlated with stage (p = 0.017). TARS was secreted by ovarian cancer cells, and patient serum TARS was related to tumor TARS and angiogenic markers, but did not achieve significance with respect to stage. Multivariate Cox proportional hazard models revealed a surprising inverse relationship between TARS expression and mortality risk in late stage disease (p = 0.062). CONCLUSIONS:
TARS expression is increased in epithelial ovarian cancer and correlates with markers of angiogenic progression. These findings and the association of TARS with disease survival provide clinical validation that TARS is associated with angiogenesis in ovarian cancer. These results encourage further study of TARS as a regulator of the tumor microenvironment and possible target for diagnosis and/or treatment in ovarian cancer.
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Authors | Theresa L Wellman, Midori Eckenstein, Cheung Wong, Mercedes Rincon, Takamaru Ashikaga, Sharon L Mount, Christopher S Francklyn, Karen M Lounsbury |
Journal | BMC cancer
(BMC Cancer)
Vol. 14
Pg. 620
(Aug 27 2014)
ISSN: 1471-2407 [Electronic] England |
PMID | 25163878
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- Tumor Necrosis Factor-alpha
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Threonine-tRNA Ligase
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Topics |
- Biomarkers, Tumor
(metabolism)
- Carcinoma, Ovarian Epithelial
- Cell Line, Tumor
- Female
- Humans
- Neoplasms, Glandular and Epithelial
(metabolism, mortality, pathology, physiopathology)
- Neovascularization, Pathologic
- Ovarian Neoplasms
(metabolism, mortality, pathology, physiopathology)
- Survival Analysis
- Threonine-tRNA Ligase
(blood, genetics, metabolism)
- Tumor Microenvironment
- Tumor Necrosis Factor-alpha
(metabolism)
- Vascular Endothelial Growth Factor A
(metabolism)
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