Author:
Meng Wenxia,Xia Qingjie,Wu Lanyan,Chen Sixiu,He Xin,Zhang Lin,Gao Qinghong,Zhou Hongmei
Abstract
Abstract
Background
The purpose of this study was to assess the expression levels for TβRI, TβRII, and TβRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TβRs in carcinogenesis of oral mucosa.
Methods
Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches.
Results
IHC signals for TβRII and TβRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TβRI, in OLK and OSCC (P > 0.05); and TβRII and TβRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-β1 led to a remarkable decrease in the expression of TβRII and TβRIII in CAFs (P < 0.05).
Conclusion
This study provides the first evidence that the loss of TβRII and TβRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TβRII and TβRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference24 articles.
1. Elliott RL, Blobe GC: Role of transforming growth factor Beta in human cancer. J Clin Oncol. 2005, 23: 2078-2093. 10.1200/JCO.2005.02.047.
2. Attisano L, Wrana JL: Signal transduction by the TGF-beta superfamily. Science. 2002, 296: 1646-1647. 10.1126/science.1071809.
3. Goggins M, Shekher M, Turnacioglu K, Yeo CJ, Hruban RH, Kern SE: Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas. Cancer Res. 1998, 58: 5329-5332.
4. Munoz-Antonia T, Muro-Cacho C, Sharma S, Cantor A, Bepler G: Expression of TGFbeta type-II receptor in association with markers of proliferation and apoptosis in premalignant lung lesions. Cancer. 2007, 110: 1527-1531. 10.1002/cncr.22937.
5. Turley RS, Finger EC, Hempel N, How T, Fields TA, Blobe GC: The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer. Cancer Res. 2007, 67: 1090-1098. 10.1158/0008-5472.CAN-06-3117.
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