Abstract
Abstract OBJECTIVES: The recent advances in understanding the relation between cancer and metabolism have highlighted the relevance of serine/glycine biosynthesis and one-carbon metabolism. The aim of this study was to evaluate the expression of enzymes associated with serine/glycine metabolism in ovarian cancer stem like cells (CSCs) and discuss their potential clinical implications. METHODS: We established primary ovarian cancer cell cultures from dissected fresh tumor tissue. To isolate CD117(+) and CD44(+) CSCs from primary ovarian cancer cultures, we have modified and optimized the Magnetic-Activated Cell Sorting (MACS) procedure from Miltenyi resulting in high sorting purity. In the present study, we used Western blotting and immunohistochemistry to examine three serine-/glycine-metabolism-associated proteins (PHGDH, SHMT, and GLDC) in CSCs and ovarian cancer cases using tissue microarray (TMA). The expression of stemness gene (Nanog, Oct3/4, Sox2 and ABCG2) mRNA was determined by RT-PCR and protein expression was detected by Western blot analysis. RESULTS: GLDC, PHGDH and SHMT, associated with serine/ glycine metabolism, showed lower expression in the CSCs. TMA showed that the different expressions of GLDC, PHGDH and SHMT in platinum-sensitive and platinum-resistant ovarian cancer cases (p<0.004). GLDC mRNA was most frequently expressed in primary ovarian cancer culture cells. By Cox multivariate analysis, tumor SHMT1 negativity (HR: 2.132, 95% CI: 1.229-3.664, p = 0.007) was associated with short overall survival. CONCLUSIONS: Based on our findings, we concluded that the expression of serine-metabolism-associated proteins was related with resistance of ovarian cancer cells and patient's survival. Citation Format: So-Jin Shin, Hye-Won Chung, Hyun-Gyo Lee, Eun Som Choi, Chi-Heum Cho. Differential expression of enzymes associated with glycine metabolism in ovarian cancer stem like cell. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1147. doi:10.1158/1538-7445.AM2015-1147
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