BackgroundThe 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.MethodsNormal 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.ResultsIHC 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).ConclusionThis 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.

The NF-κB signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future.

The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-b receptor III (TbRIII) is found as an epithelialmesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TbRIII in the oral cancerous epithelial cells and their adjacent carcinoma-associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TbRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies. Cancer Res; 74(8); 2306-15. Ó2014 AACR.