Introduction

Canine urothelial carcinoma (UC) is the most common form of canine bladder cancer. Despite a variety of treatment options, patients still succumb to local disease progression and/or metastatic spread. Monoacylglycerol lipase (MAGL) is a serine hydrolase that mediates metabolism of endogenous cannabinoids. Overexpression of MAGL in several human malignancies has been associated with more aggressive and invasive tumors as it may comprise a crucial metabolic network that supports epithelial to mesenchymal transition. Our objectives were to evaluate expression of MAGL in canine UC cell lines and assess the effects of MAGL inhibition on UC phenotype.

Methods

Three canine UC cell lines (AXA, SH, and Orig) and one non-cancer canine cell line, MDCK, were evaluated. MAGL expression was assessed via Western blotting. Inhibition of MAGL was conducted with specific chemical inhibitors and DsiRNA. The half maximal inhibitory concentration for inhibitors was established using crystal violet assay. Migration and invasion capacity were assessed using transwell assays with and without Matrigel coating.

Results

MAGL expression was detected in all three UC cell lines, while MDCK showed minimal expression. AXA and Orig demonstrated low expression while SH showed high [removed] p<0.001). Furthermore, SH demonstrated a greater migration capacity (p<0.0001) compared to AXA and Orig. Both chemical and DsiRNA inhibition of MAGL attenuated (p<0.01) migration and invasion capacity in SH and AXA cells.

Conclusion

Targeted inhibition of MAGL in canine UC is worthy of further investigation as a therapeutic option to potentially improve outcome of patients.

Funding Information

This study was funded by a Pet Trust Operating Grant to Dr. Sam E. Hocker.