Fatty Acid Amide Hydrolase in Prostate Cancer: Association with Disease Severity and Outcome, CB1 Receptor Expression and Regulation by IL-4
Open Access
- 19 August 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (8), e12275
- https://doi.org/10.1371/journal.pone.0012275
Abstract
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.Keywords
This publication has 64 references indexed in Scilit:
- The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in AstrocytomasPLOS ONE, 2010
- Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer PathogenesisCell, 2010
- Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2British Journal of Cancer, 2009
- A high cannabinoid CB1 receptor immunoreactivity is associated with disease severity and outcome in prostate cancerEuropean Journal Of Cancer, 2009
- Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor GrowthCancer Research, 2008
- Expression and function of fatty acid amide hydrolase in prostate cancerInternational Journal of Cancer, 2008
- Analysis of Promoter Regions Regulating Basal and Interleukin-4-Inducible Expression of the Human CB1 Receptor Gene in T LymphocytesMolecular Pharmacology, 2007
- Cannabinoids in pancreatic cancer: Correlation with survival and painInternational Journal of Cancer, 2007
- Diverse roles of 2‐arachidonoylglycerol in invasion of prostate carcinoma cells: Location, hydrolysis and 12‐lipoxygenase metabolismInternational Journal of Cancer, 2007
- Cannabinoid Receptor Agonist-induced Apoptosis of Human Prostate Cancer Cells LNCaP Proceeds through Sustained Activation of ERK1/2 Leading to G1 Cell Cycle ArrestPublished by Elsevier BV ,2006