Secreted TGF-beta-induced protein promotes aggressive progression in bladder cancer cells
Received 16 March 2019
Accepted for publication 5 July 2019
Published 25 July 2019 Volume 2019:11 Pages 6995—7006
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
Jun Zou,1,* Ruiyan Huang,2,* Huajun Li,1 Bin Wang,3 Yanfei Chen,3 Shuwei Chen,4 Kaifu Ou,4,† Xutao Wang4
1Department of Emergency Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Ultrasonography and Electrocardiograms, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Department of Urology, Affiliated Cancer Hospital & Institue of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4The Third Clinical College of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China
†Kaifu Ou passed away on March 8, 2019.
*These authors contributed equally to this work
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.
Keywords: TGFBI, invasive progression, EMT, secreted protein, tumor markers, bladder cancer
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