4.4 Article

Metabolomic characterization of experimental ovarian cancer ascitic fluid

期刊

METABOLOMICS
卷 13, 期 10, 页码 -

出版社

SPRINGER
DOI: 10.1007/s11306-017-1254-3

关键词

Ovarian cancer; Ascitic fluid; Orthotopic tumor implantation; Metabolites; High-resolution proton NMR; Cancer cells; Conditioned culture media

资金

  1. Tina's Wish Foundation
  2. NIH [P50CA013175, R01CA193365, R01CA136576, P30CA06973]

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Introduction Malignant ascites (MA) is a major cause of morbidity that occurs in 37% of ovarian cancer patients. The accumulation of MA in the peritoneal cavity due to cancer results in debilitating symptoms and extremely poor quality of life. There is an urgent unmet need to expand the understanding of MA to design effective treatment strategies, and to improve MA diagnosis. Objective Our purpose here is to contribute to a better characterization of MA metabolic composition in ovarian cancer. Method We determined the metabolic composition of ascitic fluids resulting from orthotopic growth of two ovarian cancer cell lines, the mouse ID8-vascular endothelial growth factor (VEGF)-Defb29 cell line and the human OVCAR3 cell line using high-resolution H-1 MRS. ID8VEGF-Defb29 tumors induce large volumes of ascites, while OVCAR3 tumors induce ascites less frequently and at smaller volumes. To better understand the factors driving he metabolic composition of the fluid, we characterized the metabolism of these ovarian cancer cells in culture by analyzing cell lysates and conditioned culture media with H-1 NMR. Results Distinct metabolite patterns were detected in ascitic fluid collected from OVCAR3 and ID8-VEGFDefb29 tumor bearing mice that were not reflected in the corresponding cell culture or conditioned medium. Conclusion High-resolution H-1 NMR metabolic markers of MA can be used to improve characterization and diagnosis of MA. Metabolic characterization of MA can provide new insights into how MA fluid supports cancer cell growth and resistance to treatment, and has the potential to identify metabolic targeting strategies to reduce or eliminate the formation of MA.

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