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J Pathol. 2015 Aug;236(4):517-30. doi: 10.1002/path.4547.

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy.

Author information

1
Uro-oncology Research Group, Cancer Research UK (CRUK) Cambridge Institute, Cambridge, UK.
2
Department of Morphology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, Brazil.
3
Department of Pathology, Centro Hospitalar do Porto, Portugal.
4
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
5
Life and Health Sciences Research Institute (ICVS), School of Health Sciences,University of Minho, Braga, Portugal.
6
ICVS/3Bs-PT Government Associate Laboratory, Braga/Guimaraes, Portugal.
7
Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal.
8
Department of Pathology and Oncology, Medical Faculty of the University of Porto, Portugal.
9
Department of Urology, University of Cambridge, and S4, Department of Oncology, Addenbrooke's Hospital, Cambridge, UK.

Abstract

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.

KEYWORDS:

cell metabolism; metabolic targets; monocarboxylate transporters; poor prognosis markers; prostate cancer

PMID:
25875424
PMCID:
PMC4528232
DOI:
10.1002/path.4547
[Indexed for MEDLINE]
Free PMC Article

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