title: Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans.
abstract: OBJECTIVE
  Endocannabinoids may modify cancer development, progression and associated pain. We determined whether cancer-evoked dysregulations in this system become manifest in altered tissue and plasma endocannabinoids.
  
  
  METHODS
  Endocannabinoid changes due to cancer were explored in a local and metastatic syngeneic mouse melanoma model. Endocannabinoid stratification in human cancer was cross-sectionally assessed in the plasma of 304 patients (147 men, 157 women, aged 32 - 87 years) suffering from several types of cancer at Roman Numeral Staging between I and IVc, mostly IV (n = 220), and compared with endocannabinoids of healthy controls.
  
  
  RESULTS
  In mice with local tumor growth, ethanolamide endocannabinoids, i.e., anandamide (AEA), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were downregulated, whereas 2-arachidonoylglycerol (2-AG) was increased. Upon spreading of the cancer cells particularly 2-AG steadily increased in parallel to disease progression while OEA modulated cell migration. Results translated into humans, in whom cancer was associated with a decreased AEA, increased 2-AG and increased OEA correlating with the number of metastases.
  
  
  CONCLUSIONS
  The endocannabinoid system was subject to cancer-associated regulations to an extent that led to measurable changes in circulating endocannabinoid levels, emphasizing the importance of the endocannabinoid system in the pathophysiology of cancer.
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sailler
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitz
authors.affiliation: Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt am Main, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreiros
authors.affiliation: Occupational Health Service, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wicker
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Zschiebsch
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Geethanjali
authors.initials: G
authors.lastname: Pickert
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Walter
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Tegeder
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
keywords: Cannabinoids; Human; Metastasis; Mice