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Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging
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 quantif...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843602/ https://www.ncbi.nlm.nih.gov/pubmed/29520098 http://dx.doi.org/10.1038/s41598-018-22480-w |
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author | Martinez, Amy F. McCachren, Samuel S. Lee, Marianne Murphy, Helen A. Zhu, Caigang Crouch, Brian T. Martin, Hannah L. Erkanli, Alaattin Rajaram, Narasimhan Ashcraft, Kathleen A. Fontanella, Andrew N. Dewhirst, Mark W. Ramanujam, Nirmala |
author_facet | Martinez, Amy F. McCachren, Samuel S. Lee, Marianne Murphy, Helen A. Zhu, Caigang Crouch, Brian T. Martin, Hannah L. Erkanli, Alaattin Rajaram, Narasimhan Ashcraft, Kathleen A. Fontanella, Andrew N. Dewhirst, Mark W. Ramanujam, Nirmala |
author_sort | Martinez, Amy F. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5843602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58436022018-03-14 Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging Martinez, Amy F. McCachren, Samuel S. Lee, Marianne Murphy, Helen A. Zhu, Caigang Crouch, Brian T. Martin, Hannah L. Erkanli, Alaattin Rajaram, Narasimhan Ashcraft, Kathleen A. Fontanella, Andrew N. Dewhirst, Mark W. Ramanujam, Nirmala Sci Rep Article 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. Nature Publishing Group UK 2018-03-08 /pmc/articles/PMC5843602/ /pubmed/29520098 http://dx.doi.org/10.1038/s41598-018-22480-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Martinez, Amy F. McCachren, Samuel S. Lee, Marianne Murphy, Helen A. Zhu, Caigang Crouch, Brian T. Martin, Hannah L. Erkanli, Alaattin Rajaram, Narasimhan Ashcraft, Kathleen A. Fontanella, Andrew N. Dewhirst, Mark W. Ramanujam, Nirmala Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging |
title | Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging |
title_full | Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging |
title_fullStr | Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging |
title_full_unstemmed | Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging |
title_short | Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging |
title_sort | metaboloptics: visualization of the tumor functional landscape via metabolic and vascular imaging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843602/ https://www.ncbi.nlm.nih.gov/pubmed/29520098 http://dx.doi.org/10.1038/s41598-018-22480-w |
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