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Hyperpolarized 13C-Pyruvate Magnetic Resonance Reveals Rapid Lactate Export in Metastatic Renal Cell Carcinomas
- Source :
- Cancer research, vol 73, iss 2
- Publication Year :
- 2013
- Publisher :
- American Association for Cancer Research (AACR), 2013.
-
Abstract
- Renal cell carcinomas (RCC) are a heterogeneous group of tumors with a wide range of aggressiveness. Noninvasive methods to confidently predict the tumor biologic behavior and select appropriate treatment are lacking. Here, we investigate the dynamic metabolic flux in living RCC cells using hyperpolarized 13C-pyruvate magnetic resonance spectroscopy (MRS) combined with a bioreactor platform and interrogated the biochemical basis of the MRS data with respect to cancer aggressiveness. RCC cells have significantly higher pyruvate-to-lactate flux than the normal renal tubule cells. Furthermore, a key feature distinguishing the localized from the metastatic RCC cells is the lactate efflux rate, mediated by the monocarboxylate transporter 4 (MCT4). The metastatic RCC cells have significantly higher MCT4 expression and corresponding higher lactate efflux, which is essential for maintaining a high rate of glycolysis. We show that such differential cellular transporter expression and associated metabolic phenotype can be noninvasively assessed via real-time monitoring of hyperpolarized 13C-pyruvate-to-lactate flux. Cancer Res; 73(2); 529–38. ©2012 AACR.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Magnetic Resonance Spectroscopy
Kidney Disease
Oncology and Carcinogenesis
Cell
urologic and male genital diseases
Article
Cell Line
Kidney Tubules, Proximal
Cell Line, Tumor
Pyruvic Acid
medicine
Carcinoma
Humans
Glycolysis
Lactic Acid
Oncology & Carcinogenesis
Neoplasm Metastasis
Carcinoma, Renal Cell
Cancer
Carbon Isotopes
Tumor
biology
Proximal
Renal Cell
Transporter
medicine.disease
Kidney Tubules
medicine.anatomical_structure
Oncology
Cell culture
Monocarboxylate transporter 4
biology.protein
Flux (metabolism)
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 73
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....fe507d5e4f3bf348d9150e3375c66b23