Abstract
Most solid tumors are hypoxic in nature due to the limited supply of oxygen to internal tissues. Hypoxia plays an important role in metabolic adaptations of tumors that contribute significantly to cancer pathogenesis. Among the several metabolic alterations induced by hypoxia, hypoxia-mediated increased glucose uptake serves as the hallmark of metabolic reprogramming. Hypoxia-mediated stabilization of hypoxia-inducible factor-1 alpha (HIF-1α) transcription factor leads to altered expression of several glycolytic genes and glucose transporters, which results in increased glucose uptake by tumor cells. Here we describe an easy and simple way of measuring the hypoxia-mediated tumor glucose uptake in vivo. The method is based on fluorescent imaging probe, RediJect 2-DG, which is a nonradioactive fluorescent-tagged glucose molecule. We have discussed orthotopic tumor implantation of HIF-1α knockdown and control pancreatic cancer cells and glucose uptake measurement in vivo by using IVIS imaging system along with reagent preparations.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G (2013) Metabolic targets for cancer therapy. Nat Rev Drug Discov 12(11):829–846. https://doi.org/10.1038/nrd4145
Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314.
Zhao Y, Wieman HL, Jacobs SR, Rathmell JC (2008) Mechanisms and methods in glucose metabolism and cell death. Methods Enzymol 442:439–457. https://doi.org/10.1016/S0076-6879(08)01422-5
Plathow C, Weber WA (2008) Tumor cell metabolism imaging. J Nucl Med 49(Suppl 2):43S–63S. https://doi.org/10.2967/jnumed.107.045930
Zhu A, Lee D, Shim H (2011) Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol 38(1):55–69. https://doi.org/10.1053/j.seminoncol.2010.11.012
Bui T, Thompson CB (2006) Cancer’s sweet tooth. Cancer Cell 9(6):419–420. https://doi.org/10.1016/j.ccr.2006.05.012
Brown JM (2007) Tumor hypoxia in cancer therapy. Methods Enzymol 435:297–321. https://doi.org/10.1016/S0076-6879(07)35015-5
Wilson WR, Hay MP (2011) Targeting hypoxia in cancer therapy. Nat Rev Cancer 11(6):393–410. https://doi.org/10.1038/nrc3064
Chaika NV, Gebregiworgis T, Lewallen ME, Purohit V, Radhakrishnan P, Liu X, Zhang B, Mehla K, Brown RB, Caffrey T, Yu F, Johnson KR, Powers R, Hollingsworth MA, Singh PK (2012) MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer. Proc Natl Acad Sci U S A 109(34):13787–13792. https://doi.org/10.1073/pnas.1203339109
Mehla K, Singh PK (2014) MUC1: a novel metabolic master regulator. Biochim Biophys Acta 1845(2):126–135. https://doi.org/10.1016/j.bbcan.2014.01.001
Eales KL, Hollinshead KE, Tennant DA (2016) Hypoxia and metabolic adaptation of cancer cells. Oncogene 5:e190. https://doi.org/10.1038/oncsis.2015.50
Shukla SK, Gebregiworgis T, Purohit V, Chaika NV, Gunda V, Radhakrishnan P, Mehla K, Pipinos II, Powers R, Yu F, Singh PK (2014) Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia. Cancer Metab 2(1):18.
Abrego J, Gunda V, Vernucci E, Shukla SK, King RJ, Dasgupta A, Goode G, Murthy D, Yu F, Singh PK (2017) GOT1 -mediated anaplerotic glutamine metabolism regulates chronic acidosis stress in pancreatic cancer cells. Cancer Lett 400:37–46.
Shukla SK, Purohit V, Mehla K, Gunda V, Chaika NV, Vernucci E, King RJ, Abrego J, Goode GD, Dasgupta A, Illies AL, Gebregiworgis T, Dai B, Augustine JJ, Murthy D, Attri KS, Mashadova O, Grandgenett PM, Powers R, Ly QP, Lazenby AJ, Grem JL, Yu F, Matés JM, Asara JM, Kim J-W, Hankins JH, Weekes C, Hollingsworth MA, Serkova NJ, Sasson AR, Fleming JB, Oliveto JM, Lyssiotis CA, Cantley LC, Berim L, Singh PK (2017) MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell 32(1):71–87.e7.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Shukla, S.K., Mulder, S.E., Singh, P.K. (2018). Hypoxia-Mediated In Vivo Tumor Glucose Uptake Measurement and Analysis. In: Huang, L. (eds) Hypoxia. Methods in Molecular Biology, vol 1742. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7665-2_10
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7665-2_10
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-7664-5
Online ISBN: 978-1-4939-7665-2
eBook Packages: Springer Protocols