Open AccessMetaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging
Author(s) -
Amy F. Martinez,
Samuel S. McCachren,
Marianne Lee,
Helen Murphy,
Caigang Zhu,
Brian T. Crouch,
H Martin,
Alaattin Erkanli,
Narasimhan Rajaram,
Kathleen A. Ashcraft,
Andrew N. Fontanella,
Mark W. Dewhirst,
Nirmala Ramanujam
Publication year - 2018
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-018-22480-w
Subject(s) - in vivo , glycolysis , warburg effect , tumor microenvironment , context (archaeology) , hypoxia (environmental) , glucose uptake , pathology , metabolism , chemistry , anaerobic glycolysis , biology , cancer research , biochemistry , medicine , endocrinology , tumor cells , oxygen , insulin , paleontology , microbiology and biotechnology , organic chemistry
Many cancers adeptly modulate metabolism to thrive in fluctuating oxygen conditions; however, current tools fail to image metabolic and vascular endpoints at spatial resolutions needed to visualize these adaptations in vivo . We demonstrate a high-resolution intravital microscopy technique to quantify glucose uptake, mitochondrial membrane potential (MMP), and SO 2 to characterize the in vivo phentoypes of three distinct murine breast cancer lines. Tetramethyl rhodamine, ethyl ester (TMRE) was thoroughly validated to report on MMP in normal and tumor-bearing mice. Imaging MMP or glucose uptake together with vascular endpoints revealed that metastatic 4T1 tumors maintained increased glucose uptake across all SO 2 (“Warburg effect”), and also showed increased MMP relative to normal tissue. Non-metastatic 67NR and 4T07 tumor lines both displayed increased MMP, but comparable glucose uptake, relative to normal tissue. The 4T1 peritumoral areas also showed a significant glycolytic shift relative to the tumor regions. During a hypoxic stress test, 4T1 tumors showed significant increases in MMP with corresponding significant drops in SO 2 , indicative of intensified mitochondrial metabolism. Conversely, 4T07 and 67NR tumors shifted toward glycolysis during hypoxia. Our findings underscore the importance of imaging metabolic endpoints within the context of a living microenvironment to gain insight into a tumor’s adaptive behavior.