GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors
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Author
Ryniawec, J.M.Coope, M.R.
Loertscher, E.
Bageerathan, V.
de Oliveira Pessoa, D.
Warfel, N.A.
Cress, A.E.
Padi, M.
Rogers, G.C.
Affiliation
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of ArizonaBiostatistics and Bioinformatics Shared Resource, University of Arizona Cancer Center, University of Arizona
Issue Date
2022
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Ryniawec, J. M., Coope, M. R., Loertscher, E., Bageerathan, V., de Oliveira Pessoa, D., Warfel, N. A., Cress, A. E., Padi, M., & Rogers, G. C. (2022). GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors. Diagnostics.Journal
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Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
The microenvironment of solid tumors is dynamic and frequently contains pockets of low oxygen levels (hypoxia) surrounded by oxygenated tissue. Indeed, a compromised vasculature is a hallmark of the tumor microenvironment, creating both spatial gradients and temporal variability in oxygen availability. Notably, hypoxia associates with increased metastasis and poor survival in patients. Therefore, to aid therapeutic decisions and better understand hypoxia’s role in cancer progression, it is critical to identify endogenous biomarkers of hypoxia to spatially phenotype oncogenic lesions in human tissue, whether precancerous, benign, or malignant. Here, we characterize the glucose transporter GLUT3/SLC2A3 as a biomarker of hypoxic prostate epithelial cells and prostate tumors. Transcriptomic analyses of non-tumorigenic, immortalized prostate epithelial cells revealed a highly significant increase in GLUT3 expression under hypoxia. Additionally, GLUT3 protein increased 2.4-fold in cultured hypoxic prostate cell lines and was upregulated within hypoxic regions of xenograft tumors, including two patient-derived xenografts (PDX). Finally, GLUT3 out-performs other established hypoxia markers; GLUT3 staining in PDX specimens detects 2.6–8.3 times more tumor area compared to a mixture of GLUT1 and CA9 antibodies. Therefore, given the heterogeneous nature of tumors, we propose adding GLUT3 to immunostaining panels when trying to detect hypoxic regions in prostate samples. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Note
Open access journalISSN
2075-4418Version
Final published versionae974a485f413a2113503eed53cd6c53
10.3390/diagnostics12030676
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Except where otherwise noted, this item's license is described as Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).