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 [(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.

• Authors: Inna Serganova, Asif Rizwan, Xiaohui Ni, Sunitha B Thakur, Jelena Vider, James Russell, Ronald Blasberg, Jason A Koutcher
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 19 Pg. 6250-6261 (Oct 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21844011 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2011 AACR

Chemical References

• Isoenzymes
• RNA, Messenger
• Lactic Acid
• L-Lactate Dehydrogenase
• Lactate Dehydrogenase 5
• Glucose

Topics

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