Back to Search
Start Over
Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate Conversion and Lactate Levels In Vivo
- Source :
- Molecular Imaging and Biology. 21:86-94
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism and progression. Often PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: 1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations and/or generation of splice variants in the AR gene, and 2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors. Previously, we reported patient derived xenograft (PDX) animal models that contain characteristics of these CRPC subtypes. In this study, we have employed the PDX models to test metabolic alterations in the CRPC subtypes. PROCEDURES: Mass spectrometry and nuclear magnetic resonance analysis along with in vivo hyperpolarized 1-[(13)C]pyruvate spectroscopy experiments were performed on prostate PDX animal models. RESULTS: Using hyperpolarized 1-[(13)C]pyruvate conversion to 1-[(13)C]lactate in vivo as well as lactate measurements ex vivo, we have found increased lactate production in AR-dependent CRPC PDX models even under low-hormone levels (castrated mouse) compared to AR negative AVPC PDX models. CONCLUSIONS: Our analysis underscores the potential of hyperpolarized metabolic imaging in determining the underlying biology and in vivo phenotyping of CRPC.
- Subjects :
- Male
Cancer Research
Magnetic Resonance Spectroscopy
Cell
Mice, SCID
urologic and male genital diseases
Article
030218 nuclear medicine & medical imaging
law.invention
Mice
03 medical and health sciences
Prostate cancer
0302 clinical medicine
In vivo
Prostate
law
Pyruvic Acid
Tumor Cells, Cultured
medicine
Animals
Humans
PTEN
Neoplasm Invasiveness
Radiology, Nuclear Medicine and imaging
Lactic Acid
biology
Chemistry
Image Enhancement
medicine.disease
Magnetic Resonance Imaging
Androgen receptor
Disease Models, Animal
Prostatic Neoplasms, Castration-Resistant
medicine.anatomical_structure
Oncology
Receptors, Androgen
Disease Progression
Cancer research
biology.protein
Heterografts
Suppressor
Ex vivo
Signal Transduction
Subjects
Details
- ISSN :
- 18602002 and 15361632
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecular Imaging and Biology
- Accession number :
- edsair.doi.dedup.....566c3e8cb559f4bae82fcbe2de0a05f4