title: Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors.
abstract: OBJECTIVE
  Pro-inflammatory cytokines, growth and angiogenic factors released by leukocytes are involved in carcinogenesis and cancer progression, but they are also crucial for fighting tumour growth and spreading. We have previously demonstrated that endocannabinoids modulate cell-to-cell crosstalk during inflammation. Here, we investigated the inflammatory and tumourigenic properties of endocannabinoids in a human urinary bladder carcinoma cell line.
  
  
  METHODS
  Endocannabinoid-treated ECV304 cells were checked for tumour necrosis factor (TNF)-α secretion (by ELISA assay) and surface exposure of selectins (by in situ ELISA and FACS analysis). ECV304/Jurkat T cell interaction was assessed by adhesion and live imaging experiments. Proliferation rate, cell death and cell cycle were determined by FACS analysis.
  
  
  RESULTS
  By binding to type-1 (CB1) and type-2 (CB2) cannabinoid receptors, the endocannabinoid 2-arachidonoylglycerol (2-AG) exacerbates the pro-inflammatory status surrounding bladder carcinoma ECV304 cells, by: (i) enhancing TNF-α release, (ii) increasing surface exposure of P- and E-selectins, and (iii) allowing Jurkat T lymphocytes to adhere to treated cancer cells. We also found that the CB1 inverse agonist AM281, unlike 2-AG, decreases cancer proliferation by delaying cell cycle progression.
  
  
  CONCLUSIONS
  Our data suggest that 2-AG modulates the inflammatory milieu of cancer cells in vitro, while AM281 plays a more specific role in proliferation. Collectively, these findings suggest that CB receptors may play distinct roles in cancer biology, depending on the specific ligand employed.
  
  
  CONCLUSIONS
  The in vivo assessment of the role of CB receptors in inflammation and cancer might be instrumental in broadening the understanding about bladder cancer biology.
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Gasperi
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Evangelista
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy; European Center for Brain Research (CERC)/IRCCS S. Lucia Foundation, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Oddi
authors.affiliation: European Brain Research Institute (EBRI), Rome, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Florenzano
authors.affiliation: European Center for Brain Research (CERC)/IRCCS S. Lucia Foundation, Rome, Italy; Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Chiurchiù
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Avigliano
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Rome, Italy. Electronic address: catani@uniroma2.it.
authors.forename: M Valeria
authors.initials: MV
authors.lastname: Catani
authors.affiliation: European Center for Brain Research (CERC)/IRCCS S. Lucia Foundation, Rome, Italy; Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy. Electronic address: m.maccarrone@unicampus.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D002186:Cannabinoids / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D019169:Jurkat Cells; D019041:L-Selectin / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects*; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin
keywords: Cancer; Cannabinoid receptors; Endocannabinoids; Inflammation; Proliferation