title: A role for oleoylethanolamide in chronic lymphocytic leukemia.
abstract: Oleoylethanolamide (OEA) is a bioactive lipid that stimulates nuclear and G protein-coupled receptors and regulates appetite and fat metabolism. It has not previously been shown to have a role in cancer. However, a mass spectrometry-based lipidomics platform revealed the presence of high amounts of OEA in the plasma of chronic lymphocytic leukemia (CLL) patients compared with normal donors. CLL cells produced OEA and the magnitude of plasma OEA levels was related directly to the circulating leukemic cell number. OEA from CLL cells was increased by URB-597, an inhibitor of fatty acid amide hydrolase (FAAH), and decreased by inflammatory mediators that downregulate expression of N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD). These enzymes degrade and synthesize OEA, respectively. Nonphysiologic doses of OEA prevented spontaneous apoptosis of CLL cells in a receptor-independent manner that was mimicked by its free fatty acid (FFA) derivative oleate. However, OEA-containing supernatants from CLL cells induced lipolysis in adipocytes, lipid products from adipocytes protected CLL cells from cytotoxic chemotherapy, and increased levels of FFAs were found in CLL plasma that correlated with OEA. We suggest OEA is a lipolytic factor produced by CLL cells to fuel their growth with a potential role in drug resistance and cancer cachexia.
authors.affiliation: 1] Nestlé Institute of Health Sciences, Lausanne, Switzerland [2] Medical Research Council, Cambridge, UK [3] Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Masoodi
authors.affiliation: Biology Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.affiliation: 1] Medical Research Council, Cambridge, UK [2] Metabolomx, Mountain View, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Eiden
authors.affiliation: Biology Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bahlo
authors.affiliation: Biology Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
authors.forename: R B
authors.initials: RB
authors.lastname: Ceddia
authors.affiliation: Inception Sciences, Inc., San Diego, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Baccei
authors.affiliation: Inception Sciences, Inc., San Diego, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Prasit
authors.affiliation: 1] Biology Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada [3] Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada [4] Department of Medicine, University of Toronto, Toronto, Ontario, Canada [5] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D E
authors.initials: DE
authors.lastname: Spaner
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000378:metabolism; D016022:Case-Control Studies; D002470:Cell Survival; D002478:Cells, Cultured; D063388:Endocannabinoids; D005260:Female; D006801:Humans; D006868:Hydrolysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019301:Oleic Acid / Q000378:metabolism; D009829:Oleic Acids / Q000097:blood / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D019301:Oleic Acid; D009829:Oleic Acids; D000099252:Fatty Acid Amide Hydrolases; C488250:oleoylethanolamide