<p>Secreted TGF-beta-induced protein promotes aggressive progression in bladder cancer cells</p>

Abstract

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-muscle-invasive 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 up-regulation 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.

TGFBI Protein Is Increased in the Urine of Patients with High-Grade Urothelial Carcinomas, and Promotes Cell Proliferation and Migration

“…Although the molecular background responsible for the high expression of TGFBI in high-grade UC remains elusive, our in vitro results obtained in 5637 cells demonstrate that TGFBI clearly holds an independent and, most likely, unfavorable role in the progression of UC. Our results are corroborated by Zou and colleagues who, very recently, proved a significantly increased level of TGFBI mRNA and protein in the tissues of patients with muscle invasive bladder cancers and showed that a high TGFBI tissue expression was correlated with the histological grade and clinical stage [41].…”

TGF-β and microRNA Interplay in Genitourinary Cancers

“…TGFBI is secreted by bladder cancer cells to induce proliferation, migration, and invasion, as well as EMT in an autocrine manner. Moreover, TGFBI overexpression stimulates the growth of bladder cancer xenografts in mice [206]. Interestingly, enhanced TGF-β1 expression was suggested as a mechanism mediating cancerous effects of chronic long-term low-dose ionizing radiation exposure [207].…”

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

“…Some researchers 44,45 have demonstrated the linkage between DPYSL2 and mTOR signaling pathway, and the activation of mTOR signaling pathway is crucial for T cell differentiation 46 , suggesting the potential function of DPYSL2 in immunobiology of bladder cancer. TFGBI is an exocrine protein and could promote the malignant phenotypes of BLCA 47,48 . Recent study 49 has identi ed TGFBI as an immune-relevant biomarker for prognosis of clear cell renal cell carcinoma based on multiple datasets, verifying our interesting ndings.…”