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Metabolomic characterization of experimental ovarian cancer ascitic fluid

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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.

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Abbreviations

Chk:

Choline kinase

Cho:

Free choline

CSI:

Chemical shift imaging

GPC:

Glycerophosphocholine

PC:

Phosphocholine

PtCho:

Phosphatidylcholine

PUFA:

Poly unsaturated fatty acids

tCho:

Total choline

VEGF:

Vascular endothelial growth factor

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Acknowledgements

This work was supported by grants from the Tina’s Wish Foundation, by NIH P50CA013175, R01CA193365, R01CA136576 and P30CA06973.

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Authors and Affiliations

  1. Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 212 Traylor Building, 720 Rutland Avenue, Baltimore, MD, 21205, USA

    Santosh K. Bharti, Flonné Wildes, Zaver M. Bhujwalla & Marie-France Penet

  2. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Chien-Fu Hung & T. C. Wu

  3. Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Zaver M. Bhujwalla & Marie-France Penet

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  1. Santosh K. Bharti
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  2. Flonné Wildes
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  3. Chien-Fu Hung
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  4. T. C. Wu
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  5. Zaver M. Bhujwalla
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Correspondence to Marie-France Penet.

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Bharti, S.K., Wildes, F., Hung, CF. et al. Metabolomic characterization of experimental ovarian cancer ascitic fluid. Metabolomics 13, 113 (2017). https://doi.org/10.1007/s11306-017-1254-3

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