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Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-4
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 8, e12275- p.Article in journal (Refereed) Published
Abstract [en]

Background

Recent data have indicated that there may be a dysregulation of endocannabinoid metabolism in cancer. Here we have investigated the expression of the endocannabinoid metabolising enzyme fatty acid amide hydrolase (FAAH) in a well characterised tissue microarray from patients diagnosed with prostate cancer at transurethral resection for voiding problems.

Methodology/Principal Findings

FAAH immunoreactivity (FAAH-IR) was assessed in formalin-fixed paraffin-embedded non-malignant and tumour cores from 412 patients with prostate cancer. CB1 receptor immunoreactivity (CB1IR) scores were available for this dataset. FAAH-IR was seen in epithelial cells and blood vessel walls but not in the stroma. Tumour epithelial FAAH-IR was positively correlated with the disease severity at diagnosis (Gleason score, tumour stage, % of the specimen that contained tumour) for cases with mid-range CB1IR scores, but not for those with high CB1IR scores. For the 281 cases who only received palliative therapy at the end stages of the disease, a high tumour epithelial FAAH-IR was associated with a poor disease-specific survival. Multivariate Cox proportional-hazards regression analyses indicated that FAAH-IR gave additional prognostic information to that provided by CB1IR when a midrange, but not a high CB1IR cutoff value was used. Interleukin-4 (IL-4) receptor IR was found on tumour epithelial cells and incubation of prostate cancer PC-3 and R3327 AT1 cells with IL-4 increased their FAAH activity.

Conclusions/Significance

Tumour epithelial FAAH-IR is associated with prostate cancer severity and outcome at mid-range, but not high, CB1IR scores. The correlation with CB1IR in the tumour tissue may be related to a common local dysregulation by a component of the tumour microenvironment.

Place, publisher, year, edition, pages
Public Library of Science , 2010. Vol. 5, no 8, e12275- p.
National Category
Pathobiology
Research subject
Pathology
Identifiers
URN: urn:nbn:se:umu:diva-40759DOI: 10.1371/journal.pone.0012275ISI: 000281075500010PubMedID: 20808855OAI: oai:DiVA.org:umu-40759DiVA: diva2:402666
Available from: 2011-03-09 Created: 2011-03-09 Last updated: 2011-11-23Bibliographically approved

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Thors, LinaBergh, AndersPersson, EmmaHammarsten, PeterStattin, PärFowler, Christopher J
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