Metabolic imaging: A link between lactate dehydrogenase A, lactate, and tumor phenotype Journal Article

Authors: Serganova, I.; Rizwan, A.; Ni, X.; Thakur, S. B.; Vider, J.; Russell, J.; Blasberg, R.; Koutcher, J. A.
Article Title: Metabolic imaging: A link between lactate dehydrogenase A, lactate, and tumor phenotype
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 [ 18F]2-deoxy-2-fluoro-D-glucose positron emission tomography ([ 18F]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 [18F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors. ©2011 AACR.
Keywords: controlled study; protein expression; primary tumor; unclassified drug; cancer growth; nonhuman; positron emission tomography; animal cell; mouse; phenotype; animals; mice; breast cancer; tumor volume; oxygen; animal experiment; animal model; molecular imaging; cell line, tumor; cell type; biosynthesis; mice, nude; rna, messenger; cancer cell; fluorodeoxyglucose f 18; glucose; lactate dehydrogenase; pimonidazole; cell hypoxia; neoplasm transplantation; cancer classification; cell level; oxygen consumption; cell metabolism; l-lactate dehydrogenase; isoenzymes; proton nuclear magnetic resonance; lactic acid; mammary neoplasms, animal; glucose metabolism; lactate dehydrogenase isoenzyme 5
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 19
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-01-01
Start Page: 6250
End Page: 6261
Language: English
DOI: 10.1158/1078-0432.ccr-11-0397
PROVIDER: scopus
PUBMED: 21844011
PMCID: PMC4217119
Notes: --- - "Export Date: 2 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Ronald G Blasberg
    242 Blasberg
  2. Sunitha Bai Thakur
    42 Thakur
  3. Jason A Koutcher
    233 Koutcher
  4. James Russell
    29 Russell
  5. Jelena Vider
    31 Vider
  6. Asif Rizwan
    9 Rizwan
  7. Xiaohui Ni
    4 Ni