Dual role of TGFBR3 in bladder cancer

Liu,Xiao-Long; Xiao,Kebing; Xue,Boxin; Yang,Dongrong; Lei,Zhe; Shan,Yuxi; Zhang,Hong-Tao

doi:10.3892/or.2013.2599

Dual role of TGFBR3 in bladder cancer

Authors:
- Xiao-Long Liu
- Kebing Xiao
- Boxin Xue
- Dongrong Yang
- Zhe Lei
- Yuxi Shan
- Hong-Tao Zhang
View Affiliations

Affiliations: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: July 8, 2013 https://doi.org/10.3892/or.2013.2599
Pages: 1301-1308

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Bladder cancer is one of the most common genitourinary malignant diseases worldwide. More than 90% of bladder cancer cases are bladder urothelial carcinoma (BUC). Although transforming growth factor-β III receptor (TGFBR3) has been suggested to play a dual role in cancer progression, little is known about TGFBR3 in bladder cancer. In the present study, fresh tumor and the corresponding paracarcinoma tissue specimens were collected from 56 bladder urothelial carcinoma patients. TGFBR3 expression in these tissues was determined by western blotting. TGFBR3 was also detected in the human normal urothelial cell line SV-HUC-1, the human superficial urothelial bladder cancer cell line 5637, and the human invasive bladder cancer cell line T24 using western blotting and quantitative PCR. Cell growth, motility and invasion were also analyzed in the control and the TGFBR3 gene-silenced T24 cells. As a result, the expression of TGFBR3 was reduced (18/30) in most superficial bladder urothelial carcinoma tissues compared to the corresponding normal tissues, whereas TGFBR3 expression was more enhanced (19/26) in the invasive samples. Similarly, an increase of TGFBR3 expression was found in T24 cells, but a decrease was observed in 5637 cells. Knockdown of TGFBR3 in T24 cells resulted in decreased cell growth, motility and invasion. In conclusion, these findings suggest that TGFBR3 may play a dichotomous role in human bladder cancer, acting as both a tumor suppressor and as a tumor promoter.

View Figures

View References

1	Fleshner NE, Herr HW, Stewart AK, Murphy GP, Mettlin C and Menck HR: The National Cancer Data Base report on bladder carcinoma. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 78:1505–1513. 1996. View Article : Google Scholar : PubMed/NCBI
2	Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J and Roupret M: EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Actas Urol Esp. 36:389–402. 2012.(In Spanish).
3	Di Stasi SM, Valenti M, Verri C, Liberati E, Giurioli A, Leprini G, Masedu F, Ricci AR, Micali F and Vespasiani G: Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial. Lancet Oncol. 12:871–879. 2011.
4	DeGraff DJ, Clark PE, Cates JM, Yamashita H, Robinson VL, Yu X, Smolkin ME, Chang SS, Cookson MS, Herrick MK, Shariat SF, Steinberg GD, Frierson HF, Wu XR, Theodorescu D and Matusik RJ: Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation. PLoS One. 7:e366692012. View Article : Google Scholar : PubMed/NCBI
5	Kaufman DS, Shipley WU and Feldman AS: Bladder cancer. Lancet. 374:239–249. 2009. View Article : Google Scholar : PubMed/NCBI
6	Massague J: TGFβ in cancer. Cell. 134:215–230. 2008.
7	Gatza CE, Oh SY and Blobe GC: Roles for the type III TGF-β receptor in human cancer. Cell Signal. 22:1163–1174. 2010.
8	Siegel PM and Massague J: Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat Rev Cancer. 3:807–821. 2003.
9	Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, Kelly P, Moeller BJ, Marks JR and Blobe GC: The type III TGF-β receptor suppresses breast cancer progression. J Clin Invest. 117:206–217. 2007.
10	Turley RS, Finger EC, Hempel N, How T, Fields TA and Blobe GC: The type III transforming growth factor-β receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res. 67:1090–1098. 2007.
11	Hempel N, How T, Dong M, Murphy SK, Fields TA and Blobe GC: Loss of betaglycan expression in ovarian cancer: role in motility and invasion. Cancer Res. 67:5231–5238. 2007. View Article : Google Scholar : PubMed/NCBI
12	Gordon KJ, Dong M, Chislock EM, Fields TA and Blobe GC: Loss of type III transforming growth factor β receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression. Carcinogenesis. 29:252–262. 2008.
13	Finger EC, Turley RS, Dong M, How T, Fields TA and Blobe GC: TβRIII suppresses non-small cell lung cancer invasiveness and tumorigenicity. Carcinogenesis. 29:528–535. 2008.
14	Cooper SJ, Zou H, Legrand SN, Marlow LA, von Roemeling CA, Radisky DC, Wu KJ, Hempel N, Margulis V, Tun HW, Blobe GC, Wood CG and Copland JA: Loss of type III transforming growth factor-β receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma. Oncogene. 29:2905–2915. 2010.
15	Gatza CE, Holtzhausen A, Kirkbride KC, Morton A, Gatza ML, Datto MB and Blobe GC: Type III TGF-β receptor enhances colon cancer cell migration and anchorage-independent growth. Neoplasia. 13:758–770. 2011.
16	Ploeg M, Aben KK and Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol. 27:289–293. 2009. View Article : Google Scholar : PubMed/NCBI
17	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
18	Criswell TL, Dumont N, Barnett JV and Arteaga CL: Knockdown of the transforming growth factor-β type III receptor impairs motility and invasion of metastatic cancer cells. Cancer Res. 68:7304–7312. 2008.
19	Elliott RL and Blobe GC: Role of transforming growth factor β in human cancer. J Clin Oncol. 23:2078–2093. 2005.
20	Pardali K and Moustakas A: Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta. 1775:21–62. 2007.