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Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism.

Publication ,  Journal Article
Bose, S; Yao, H; Huang, Q; Whitaker, R; Kontos, CD; Previs, RA; Shen, X
Published in: J Ovarian Res
October 20, 2022

BACKGROUND: Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy and patients present with significant metastatic burden, particularly to the adipose-rich microenvironment of the omentum. Recent evidence has highlighted the importance of metabolic adaptations in enabling this metastasis, leading to significant interest in evolving the arsenal of tools used to study OC metabolism. In this study, we demonstrate the capability of genetically encoded fluorescent biosensors to study OC, with a focus on 3D organoid models that better recapitulate in vivo tumor microenvironments. MATERIALS AND METHODS: Plasmids encoding the metabolic biosensors HyPer, iNap, Peredox, and Perceval were transfected into 15 ovarian cancer cell lines to assay oxidative stress, NADPH/NADP+, NADH/NAD+, and ATP/ADP, respectively. Fluorescence readings were used to assay dynamic metabolic responses to omental conditioned media (OCM) and 100 μM carboplatin treatment. SKOV3 cells expressing HyPer were imaged as 2D monolayers, 3D organoids, and as in vivo metastases via an intravital omental window. We further established organoids from ascites collected from Stage III/IV OC patients with carboplatin-resistant or carboplatin-sensitive tumors (n = 8 total). These patient-derived organoids (PDOs) were engineered to express HyPer, and metabolic readings of oxidative stress were performed during treatment with 100 μM carboplatin. RESULTS: Exposure to OCM or carboplatin induced heterogenous metabolic changes in 15 OC cell lines, as measured using metabolic sensors. Oxidative stress of in vivo omental metastases, measured via intravital imaging of metastasizing SKOV3-HyPer cells, was more closely recapitulated by SKOV3-HyPer organoids than by 2D monolayers. Finally, carboplatin treatment of HyPer-expressing PDOs induced higher oxidative stress in organoids derived from carboplatin-resistant patients than from those derived from carboplatin-sensitive patients. CONCLUSIONS: Our study showed that biosensors provide a useful method of studying dynamic metabolic changes in preclinical models of OC, including 3D organoids and intravital imaging. As 3D models of OC continue to evolve, the repertoire of biosensors will likely serve as valuable tools to probe the metabolic changes of clinical importance in OC.

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Published In

J Ovarian Res

DOI

EISSN

1757-2215

Publication Date

October 20, 2022

Volume

15

Issue

1

Start / End Page

114

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Ovarian Neoplasms
  • NADP
  • NAD
  • Humans
  • Female
  • Culture Media, Conditioned
  • Carcinoma, Ovarian Epithelial
  • Carboplatin
  • Biosensing Techniques
 

Citation

APA
Chicago
ICMJE
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Bose, S., Yao, H., Huang, Q., Whitaker, R., Kontos, C. D., Previs, R. A., & Shen, X. (2022). Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism. J Ovarian Res, 15(1), 114. https://doi.org/10.1186/s13048-022-01046-5
Bose, Shree, Haipei Yao, Qiang Huang, Regina Whitaker, Christopher D. Kontos, Rebecca A. Previs, and Xiling Shen. “Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism.J Ovarian Res 15, no. 1 (October 20, 2022): 114. https://doi.org/10.1186/s13048-022-01046-5.
Bose S, Yao H, Huang Q, Whitaker R, Kontos CD, Previs RA, et al. Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism. J Ovarian Res. 2022 Oct 20;15(1):114.
Bose, Shree, et al. “Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism.J Ovarian Res, vol. 15, no. 1, Oct. 2022, p. 114. Pubmed, doi:10.1186/s13048-022-01046-5.
Bose S, Yao H, Huang Q, Whitaker R, Kontos CD, Previs RA, Shen X. Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism. J Ovarian Res. 2022 Oct 20;15(1):114.
Journal cover image

Published In

J Ovarian Res

DOI

EISSN

1757-2215

Publication Date

October 20, 2022

Volume

15

Issue

1

Start / End Page

114

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Ovarian Neoplasms
  • NADP
  • NAD
  • Humans
  • Female
  • Culture Media, Conditioned
  • Carcinoma, Ovarian Epithelial
  • Carboplatin
  • Biosensing Techniques