Secreted TGF-beta-induced protein promotes aggressive progression in bladder cancer cells.

Background: Transforming growth factor-beta-induced (TGFBI) is an exocrine protein, which has been found to be able to promote the development of nasopharyngeal carcinoma, glioma, pancreatic cancer, and other tumors. However, there is currently no report concerning the relationship between TGFBI and invasive progression of bladder cancer (BCa). Methods: IHC staining, qRT-PCR and Western blot were used to analyze TGFBI and EMT markers levels. In vivo tumorigenesis was performed by xenograft tumor model. Results: In this study, we found that both mRNA and protein levels of TGFBI were significantly up-regulated in muscle invasive bladder cancer (MIBC) tissues compared with non-muscleinvasive bladder cancer (NMIBC) tissues. The high expression level of TGFBI was positively correlated with high histological grade and advanced clinical stage, and BCa patients with high TGFBI levels exhibited poor prognoses. We further confirmed that high expression level of TGFBI can promote proliferation, invasive progression, and epithelial-to-mesenchymal transition (EMT) of BCa cells in vitro, as well as promote tumor growth and EMT in vivo, while silencing of TGFBI inhibited these malignant phenotypes. TGFBI was involved in the upregulation of EMT by inducing the expression level of Slug, Vimentin, Snail, MMP2, and MMP9 genes, while it down-regulated the expression level of E-cadherin. Moreover, Western blot analysis was carried out to demonstrate that BCa cell lines stably transfected with expression of TGFBI, a secreted protein. Furthermore, conditional medium containing TGFBI protein also resulted in enhanced EMT and malignant phenotype of BCa cells. Conclusion: Our results indicate that high expression level of TGFBI promotes EMT, proliferation, and invasive progression of BCa cells, and TGFBI is a potential therapeutic target and prognostic marker for BCa.