PreprintArticleVersion 1This version is not peer-reviewed
Multimodal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy
Version 1
: Received: 23 September 2024 / Approved: 24 September 2024 / Online: 25 September 2024 (11:17:44 CEST)
How to cite:
Erickson-Bhatt, S.; Cox, B. L.; Macdonald, E.; Chacko, J. V.; Begovatz, P.; Keely, P.; Ponik, S. M.; Eliceiri, K. W.; Fain, S. B. Multimodal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy. Preprints2024, 2024091865. https://doi.org/10.20944/preprints202409.1865.v1
Erickson-Bhatt, S.; Cox, B. L.; Macdonald, E.; Chacko, J. V.; Begovatz, P.; Keely, P.; Ponik, S. M.; Eliceiri, K. W.; Fain, S. B. Multimodal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy. Preprints 2024, 2024091865. https://doi.org/10.20944/preprints202409.1865.v1
Erickson-Bhatt, S.; Cox, B. L.; Macdonald, E.; Chacko, J. V.; Begovatz, P.; Keely, P.; Ponik, S. M.; Eliceiri, K. W.; Fain, S. B. Multimodal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy. Preprints2024, 2024091865. https://doi.org/10.20944/preprints202409.1865.v1
APA Style
Erickson-Bhatt, S., Cox, B. L., Macdonald, E., Chacko, J. V., Begovatz, P., Keely, P., Ponik, S. M., Eliceiri, K. W., & Fain, S. B. (2024). Multimodal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy. Preprints. https://doi.org/10.20944/preprints202409.1865.v1
Chicago/Turabian Style
Erickson-Bhatt, S., Kevin W Eliceiri and Sean B Fain. 2024 "Multimodal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy" Preprints. https://doi.org/10.20944/preprints202409.1865.v1
Abstract
Despite the role of metabolism in breast cancer metastasis, we still cannot predict which breast tumors will progress to distal metastatic lesions or remain dormant. This work uses metabolic imaging to study breast cancer cell lines (4T1, 4T07, and 67NR) with differing metastatic potential in a 3D collagen gel bioreactor system. Within the bioreactor, hyperpolarized magnetic resonance spectroscopy (HP-MRS) is used to image lactate/pyruvate ratios, while fluorescence lifetime imaging microscopy (FLIM) of endogenous metabolites measures metabolism at the cellular scale. HP-MRS results showed no lactate peak for 67NR and a comparatively large lactate/pyruvate ratio for both 4T1 and 4T07 cell lines, suggestive of greater pyruvate utilization with greater metastatic potential. Similar patterns were observed using FLIM with significant increases in FAD intensity, redox ratio, and NAD(P)H lifetime. The lactate/pyruvate ratio was strongly correlated to NAD(P)H lifetime, consistent with the role of NADH as an electron donor for the glycolytic pathway, suggestive of an overall upregulation of metabolism (both glycolytic and oxidative), for the 4T07 and 4T1 cell lines compared to the non-metastatic 67NR cell line. These findings support a complementary role for HP-MRS and FLIM enabled by a novel collagen gel bioreactor system to investigate metastatic potential and cancer metabolism.
Keywords
breast cancer; metastatic potential; metabolism; FLIM; MRSI; hyperpolarized; carbon-13
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.