TGF-β type III receptor (TGFBR3), a co-receptor for TGF-β family members, is required for the high-affinity binding of ligands to their receptors to begin their cellular function. More and more studies showed contrasting roles of TGFBR3, tumor suppressor or oncogene, depending on the cancer type. However, the exact role of TGFBR3 and the responsible mechanism in oral cancer remains to be characterized. By using immunohisotochemical staining and real-time PCR, we found a down-regulation of TGFBR3 in oral cancer tissues. In the same line of this observation, we also detected a significant decrease of soluble TGFBR3 (sTGFBR3) in the oral cancer patient sera when compared with normal sera. Using Kaplan Meyer survival curve analysis and log rank test, we found that low TGFBR3 expression patients tend to have poor clinical outcome than those with high expression. Genetic manipulation of TGFBR3 was used to examine the role of TGFBR3 in oral cancer cells. Although the alteration resulted in differential effects on cell proliferation, TGFBR3 knockdown significantly increased migration and Matrigel invasion. TGFBR3 overexpression had the opposite effect on cell migration and invasion. Xenograft tumorigenesis and metastasis will be used to confirm the effect observed in vitro. Since TGFB is frequently overxpressed in oral cancer cells, we will evaluate the therapeutic potential of using sTGFBR3 in treating oral cancer in mice. Our study should facilitate studying the role of TGFBR3 in oral cancer progression and metastasis, and evaluating the possibility of using TGFBR3 as a therapeutic target for oral cancer treatment.
Date:
2013-04
Relation:
Cancer Research. 2013 Apr;73(8 Suppl. 1):Abstract number 3987.
