Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism

The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were...

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Bibliographic Details
Published in:Scientific reports 2017-02, Vol.7 (1), p.42157-42157, Article 42157
Main Authors: Bettiga, Arianna, Aureli, Massimo, Colciago, Giorgia, Murdica, Valentina, Moschini, Marco, Lucianò, Roberta, Canals, Daniel, Hannun, Yusuf, Hedlund, Petter, Lavorgna, Giovanni, Colombo, Renzo, Bassi, Rosaria, Samarani, Maura, Montorsi, Francesco, Salonia, Andrea, Benigni, Fabio
Format: Article
Language:English
Subjects:
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AKT protein
Apoptosis
Biosynthesis
Bladder cancer
Cancer
Cannabinoid CB1 receptors
Cannabinoid CB2 receptors
Caspase
Caspase-3
Ceramide
Cytoskeleton
Gene silencing
Humanities and Social Sciences
Immunohistochemistry
Labeling
Metabolism
Motility
multidisciplinary
Science
Sphingolipids
Sphingosine 1-phosphate
Src protein
Tumor cell lines
Tumors
Urinary bladder
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Summary:The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour. Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism. Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements. CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p 
ISSN:2045-2322
2045-2322
DOI:10.1038/srep42157