Journal article
Multi-Modal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy
Metabolites, Vol.14(10), 550
10/15/2024
DOI: 10.3390/metabo14100550
PMCID: PMC11509230
PMID: 39452931
Abstract
Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
Details
- Title: Subtitle
- Multi-Modal Investigation of Metabolism in Murine Breast Cancer Cell Lines Using Fluorescence Lifetime Microscopy and Hyperpolarized 13C-Pyruvate Magnetic Resonance Spectroscopy
- Creators
- Sarah Erickson-Bhatt - Morgridge Institute for ResearchBenjamin L. Cox - Morgridge Institute for ResearchErin Macdonald - University of Wisconsin–MadisonJenu V. Chacko - University of Wisconsin–MadisonPaul Begovatz - University of Wisconsin–MadisonPatricia J. Keely - University of Wisconsin–MadisonSuzanne M. Ponik - University of Wisconsin–MadisonKevin W. Eliceiri - Morgridge Institute for ResearchSean B. Fain - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Metabolites, Vol.14(10), 550
- Publisher
- MDPI
- DOI
- 10.3390/metabo14100550
- PMID
- 39452931
- PMCID
- PMC11509230
- ISSN
- 2218-1989
- eISSN
- 2218-1989
- Grant note
- Morgridge Institute for Research Postdoctoral ProgramUW Carbone Cancer Center, CCSG: P30CA014520, T32 CA009206 Wisconsin Alumni Research Foundation
We acknowledge funding from the Morgridge Institute for Research Postdoctoral Program (S.E.-B.), NIH U54 CA268069 (S.M.P., K.W.E.), R01CA179556 (S.M.P.), the UW Carbone Cancer Center, CCSG P30CA014520 (S.B.F.), the T32 CA009206 fellowship to Dr. Paul Begovatz, the Office of the Vice Chancellor for Research and Graduate Education at the University of Wisconsin-Madison (S.B.F.), and the Wisconsin Alumni Research Foundation (S.B.F.).
- Language
- English
- Date published
- 10/15/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Health and Human Physiology
- Record Identifier
- 9984737460202771
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