This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schroeder, T. Articles by Dewhirst, M. W. Search for Related Content PubMed PubMed Citation Articles by Schroeder, T. Articles by Dewhirst, M. W.

Spatial Heterogeneity and Oxygen Dependence of Glucose Consumption in R3230Ac and Fibrosarcomas of the Fischer 344 Rat

Departments of ¹ Radiation Oncology and ² Biomedical Engineering, Duke University Medical Center, Durham, North Carolina; and ³ Texas Medical Center, Texas Heart Institute, Houston, Texas

Requests for reprints: Mark W. Dewhirst, Department of Radiation Oncology, Duke University Medical Center, Room 201 MSRB, Research Drive, Box 3455 Durham, NC 27710. Phone: 919-684-4180; Fax: 919-684-8718; E-mail: dewhirst{at}radonc.duke.edu.

To examine the oxygen-dependence of glucose consumption in solid tumors, we monitored gradients of glucose, lactate, and hypoxia in R3230Ac and FSA tumors growing in Fischer 344 rats. Bioluminescence imaging, detection of Hoechst 33342, and immunostaining of the hypoxia marker EF5 [2-8-N-(2,2,3,3,3-pentafluoropropyl)acetamide] were done in serial tumor slices. Glucose and lactate levels were also determined in liver and blood. Cells were further tested for glucose consumption and lactate production in vitro. In both tumor types, EF5 staining indicated similar maximum levels of hypoxia; the most intense staining occurred in perinecrotic regions. Glucose concentrations were highest in liver, declined from blood to tumor edge, further into vital tumor regions, and were lowest close to necrosis. Glucose was significantly lower in FSA than in R3230Ac tumors. Glucose concentrations in R3230Ac tumors were consistently higher in nonhypoxic than in hypoxic areas, with maximum values equal to systemic blood levels. Glucose in FSA tumors was close to zero, regardless of the presence or absence of hypoxia. Lactate did not differ significantly between the tumor types. FSA cells in culture showed a trend towards higher aerobic glucose consumption versus R3230Ac. Both cell lines increased their lactate production to similar levels under hypoxia. We conclude that both R3230Ac and FSA tumors retain the Pasteur effect, i.e., hypoxia triggers increased glycolysis. However, our results imply that increased aerobic glucose utilization leads to low glucose levels in FSA and a situation where supply limits uptake. This explains the repeatedly observed correlation between tumor blood flow and ¹⁸F-deoxyglucose uptake.

This article has been cited by other articles:

				R. Wirthner, S. Wrann, K. Balamurugan, R. H. Wenger, and D. P. Stiehl Impaired DNA double-strand break repair contributes to chemoresistance in HIF-1{alpha}-deficient mouse embryonic fibroblasts Carcinogenesis, December 1, 2008; 29(12): 2306 - 2316. [Abstract] [Full Text] [PDF]

				C. C. Riedl, P. Brader, P. B. Zanzonico, Y. S. Chun, Y. Woo, P. Singh, S. Carlin, B. Wen, C. C. Ling, H. Hricak, et al. Imaging Hypoxia in Orthotopic Rat Liver Tumors with Iodine 124-labeled Iodoazomycin Galactopyranoside PET Radiology, August 1, 2008; 248(2): 561 - 570. [Abstract] [Full Text] [PDF]

				M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia PNAS, December 4, 2007; 104(49): 19494 - 19499. [Abstract] [Full Text] [PDF]

				R. U. Svensson, J. M. Barnes, O. W. Rokhlin, M. B. Cohen, and M. D. Henry Chemotherapeutic Agents Up-regulate the Cytomegalovirus Promoter: Implications for Bioluminescence Imaging of Tumor Response to Therapy Cancer Res., November 1, 2007; 67(21): 10445 - 10454. [Abstract] [Full Text] [PDF]

				P. Brader, C. C. Riedl, Y. Woo, V. Ponomarev, P. Zanzonico, B. Wen, S. Cai, H. Hricak, Y. Fong, R. Blasberg, et al. Imaging of hypoxia-driven gene expression in an orthotopic liver tumor model Mol. Cancer Ther., November 1, 2007; 6(11): 2900 - 2908. [Abstract] [Full Text] [PDF]

				E. Takahashi, T. Takano, Y. Nomura, S. Okano, O. Nakajima, and M. Sato In vivo oxygen imaging using green fluorescent protein Am J Physiol Cell Physiol, October 1, 2006; 291(4): C781 - C787. [Abstract] [Full Text] [PDF]

				K. R. Laderoute, K. Amin, J. M. Calaoagan, M. Knapp, T. Le, J. Orduna, M. Foretz, and B. Viollet 5'-AMP-Activated Protein Kinase (AMPK) Is Induced by Low-Oxygen and Glucose Deprivation Conditions Found in Solid-Tumor Microenvironments. Mol. Cell. Biol., July 1, 2006; 26(14): 5336 - 5347. [Abstract] [Full Text] [PDF]

				H. Yuan, T. Schroeder, J. E. Bowsher, L. W. Hedlund, T. Wong, and M. W. Dewhirst Intertumoral Differences in Hypoxia Selectivity of the PET Imaging Agent 64Cu(II)-Diacetyl-Bis(N4-Methylthiosemicarbazone) J. Nucl. Med., June 1, 2006; 47(6): 989 - 998. [Abstract] [Full Text] [PDF]