Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer

Abstract

Background: Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients.

Objective: The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy.

Methods: The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n=248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ontoexpress).

Results: Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2.

Conclusions: The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin--an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis.

Keywords: Exosome; Urinary bladder cancer.