Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide.
Here we have investigated whether the expression levels of FAAH and CB(1) receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB(1) receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB(1)IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB(1)IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB(1)IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15year of disease-specific survival (%) of 68±7 (low endoglin, low FAAH), 45±11 (high endoglin, low FAAH), 77±6 (low endoglin, high FAAH) and 21±10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a-1b relative to stages 2-4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Dysregulated Lipid Metabolism in Cancer.
Written by:
Fowler CJ, Josefsson A, Thors L, Chung SC, Hammarsten P, Wikström P, Bergh A Are you the author?
Pharmacology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
Reference: Biochim Biophys Acta. 2012 Dec 20. pii: S1388-1981(12)00259-4(Epub ahead of print)
doi: 10.1016/j.bbalip.2012.12.005
PubMed Abstract
PMID: 23262399
