Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-4
2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 8, e12275- p.Article in journal (Refereed) Published
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.
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.
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.
Research subject Pathology
IdentifiersURN: urn:nbn:se:umu:diva-40759DOI: 10.1371/journal.pone.0012275ISI: 000281075500010PubMedID: 20808855OAI: oai:DiVA.org:umu-40759DiVA: diva2:402666