title: Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-4.
abstract: 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.
  
  
  RESULTS
  FAAH immunoreactivity (FAAH-IR) was assessed in formalin-fixed paraffin-embedded non-malignant and tumour cores from 412 patients with prostate cancer. CB(1) receptor immunoreactivity (CB(1)IR) 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 CB(1)IR scores, but not for those with high CB(1)IR 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 CB(1)IR when a midrange, but not a high CB(1)IR 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
  Tumour epithelial FAAH-IR is associated with prostate cancer severity and outcome at mid-range, but not high, CB(1)IR scores. The correlation with CB(1)IR in the tumour tissue may be related to a common local dysregulation by a component of the tumour microenvironment.
authors.affiliation: Pharmacology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Thors
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
authors.forename: Emma
authors.initials: E
authors.lastname: Persson
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
mesh_terms: D000581:Amidohydrolases / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D066246:ErbB Receptors; D015847:Interleukin-4; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases
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