Metabolomic characterization of experimental ovarian cancer ascitic fluid

Santosh K. Bharti, Flonné Wildes, Chien Fu Hung, T. C. Wu, Zaver M. Bhujwalla, Marie France Penet

Research output: Contribution to journalArticle

Abstract

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 1H MRS. ID8-VEGF-Defb29 tumors induce large volumes of ascites, while OVCAR3 tumors induce ascites less frequently and at smaller volumes. To better understand the factors driving the 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 1H NMR. Results: Distinct metabolite patterns were detected in ascitic fluid collected from OVCAR3 and ID8-VEGF-Defb29 tumor bearing mice that were not reflected in the corresponding cell culture or conditioned medium. Conclusion: High-resolution 1H 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.

LanguageEnglish (US)
Article number113
JournalMetabolomics
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Metabolomics
Ascitic Fluid
Ascites
Ovarian Neoplasms
Cells
Vascular Endothelial Growth Factor A
Tumors
Fluids
Conditioned Culture Medium
Cell culture
Bearings (structural)
Chemical analysis
Nuclear magnetic resonance
Cell growth
Metabolites
Metabolism
Culture Media
Neoplasms
Cell Line
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Metabolomic characterization of experimental ovarian cancer ascitic fluid. / Bharti, Santosh K.; Wildes, Flonné; Hung, Chien Fu; Wu, T. C.; Bhujwalla, Zaver M.; Penet, Marie France.

In: Metabolomics, Vol. 13, No. 10, 113, 01.10.2017.

Research output: Contribution to journalArticle

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N2 - 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 1H MRS. ID8-VEGF-Defb29 tumors induce large volumes of ascites, while OVCAR3 tumors induce ascites less frequently and at smaller volumes. To better understand the factors driving the 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 1H NMR. Results: Distinct metabolite patterns were detected in ascitic fluid collected from OVCAR3 and ID8-VEGF-Defb29 tumor bearing mice that were not reflected in the corresponding cell culture or conditioned medium. Conclusion: High-resolution 1H 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.

AB - 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 1H MRS. ID8-VEGF-Defb29 tumors induce large volumes of ascites, while OVCAR3 tumors induce ascites less frequently and at smaller volumes. To better understand the factors driving the 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 1H NMR. Results: Distinct metabolite patterns were detected in ascitic fluid collected from OVCAR3 and ID8-VEGF-Defb29 tumor bearing mice that were not reflected in the corresponding cell culture or conditioned medium. Conclusion: High-resolution 1H 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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