Abstract Title:

Regulation of inflammation and proliferation of human bladder carcinoma cells by type-1 and type-2 cannabinoid receptors.

Abstract Source:

Life Sci. 2015 Oct 1 ;138:41-51. Epub 2014 Oct 15. PMID: 25445433

Abstract Author(s):

Valeria Gasperi, Daniela Evangelista, Sergio Oddi, Fulvio Florenzano, Valerio Chiurchiù, Luciana Avigliano, M Valeria Catani, Mauro Maccarrone

Article Affiliation:

Valeria Gasperi


AIMS: 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.

MAIN 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.

KEY FINDINGS: 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.

SIGNIFICANCE: 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.

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