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Clinical cancer research : an official journal of the American Association for Cancer Research
Oct 01, 2011;17 (19): 6250-6261.

Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype.

Inna Serganova, Asif Rizwan, Xiaohui Ni, Sunitha B Thakur, Jelena Vider, James Russell, Ronald Blasberg, Jason A Koutcher
Author Information
  1. Inna Serganova: Department of Neurology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  2. Asif Rizwan: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  3. Xiaohui Ni: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  4. Sunitha B Thakur: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  5. Jelena Vider: Department of Neurology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  6. James Russell: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  7. Ronald Blasberg: Department of Neurology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
  8. Jason A Koutcher: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
PMID: 21844011 DOI: 10.1158/1078-0432.CCR-11-0397

Abstract

PURPOSE: We compared the metabolic profiles and the association between LDH-A expression and Lactate production in two isogenic murine breast cancer cell lines and tumors (67NR and 4T1). These cell lines were derived from a single mammary tumor and have different growth and metabolic phenotypes.
EXPERIMENTAL DESIGN: LDH-A expression, Lactate concentration, glucose utilization, and oxygen consumption were measured in cells, and the potential relationship between tumor Lactate levels [measured by magnetic resonance spectroscopic imaging (MRSI)] and tumor glucose utilization [measured by [(18)F]2-deoxy-2-fluoro-D-glucose positron emission tomography ([(18)F]FDG-PET)] was assessed in orthotopic breast tumors derived from these cell lines.
RESULTS: We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate 10-fold more Lactate than corresponding 67NR tumors. The high Lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less-intense hypoxia staining was observed in the larger 67NR tumors and is consistent with the gradual increase and plateau of Lactate concentration in enlarging 67NR tumors.
CONCLUSIONS: Lactate-MRSI has a greater dynamic range than [(18)F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors.

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Grants

  1. U24 CA083084/NCI NIH HHS
  2. P50 CA086438/NCI NIH HHS
  3. CA86438/NCI NIH HHS
  4. U24CA83084/NCI NIH HHS
  5. CA94060/NCI NIH HHS
  6. P01 CA094060/NCI NIH HHS
  7. R01 CA098505/NCI NIH HHS
  8. P01 CA115675/NCI NIH HHS
  9. CA098505/NCI NIH HHS
  10. CA115675/NCI NIH HHS
  11. P30 CA008748/NCI NIH HHS

MeSH Term

Animals
Cell Line, Tumor
Female
Glucose
Isoenzymes
L-Lactate Dehydrogenase
Lactate Dehydrogenase 5
Lactic Acid
Mammary Neoplasms, Animal
Mice
Mice, Nude
Neoplasm Transplantation
Phenotype
RNA, Messenger

Chemicals

Isoenzymes
RNA, Messenger
Lactic Acid
L-Lactate Dehydrogenase
Lactate Dehydrogenase 5
Glucose
Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.
Article has an altmetric score of 6

Word Cloud

Created with Highcharts 10.0.0lactatetumors67NR4T1tumorLDH-Aexpressionbreastcelllines[18hypoxiametabolicderivedconcentrationglucoseutilizationcellspotentiallevels[measured]F]FDG-PETorthotopicshowsmallprimarystainingPURPOSE:comparedprofilesassociationproductiontwoisogenicmurinecancersinglemammarydifferentgrowthphenotypesEXPERIMENTALDESIGN:oxygenconsumptionmeasuredrelationshipmagneticresonancespectroscopicimagingMRSIF]2-deoxy-2-fluoro-D-glucosepositronemissiontomographyassessedRESULTS:substantialdifferencenormoxiaalsogenerate10-foldcorrespondinghighassociatedintensepimonidazoleindicatorLess-intenseobservedlargerconsistentgradualincreaseplateauenlargingCONCLUSIONS:Lactate-MRSIgreaterdynamicrangemaysensitivemeasureevaluateaggressivemetastaticMetabolicimaging:linkdehydrogenasephenotype

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