Materials and methods: (1) Tissue samples were obtained from 90 previously untreated Clinical patients, including 45 oral squamous cell carcinoma (OSCC), 20 oral leukoplakia (OLK), and 25 normal tissue. The three receptors were detected by Immunohistochemical analyses. (2) 8 primary human oral CAFs and 5 primary oral NFs were attained successfully by cell culture. (3) The mRNA and protein of TbR were detected by Quantitative RT-PCR and Western blot. (4) TbRII mRNA sequencing was detected by subcloning technique. (5) The effect of exogenous TGF-b on TbR expression were also carried.
Results: (1) Immunohistochemistry for TbRII and TbRIII decreased both in tumor tissue and in tumor-associated stroma with increasing disease aggressiveness (P<0.05); No differences were observed for TbRI both in OSCC and OLK (P>0.05); (2) TbRII and TbRIII expression were also decreased in CAFs compared with NFs at both mRNA and protein level (P=0.037; P=0.031). (3) TbRII mRNA sequencing analysis reveals a change of nucleotide from C to T. (4) Exogenous TGF-b can remarkably decrease TbRII and TbRIII expression of CAFs (P=0.0062; P=0.0045).
Conclusions: For the first time, we provide evidence to define the loss of TbRII and TBRIII expression in CAFs as a common event in OSCC patients. Restoring TbRII and TbRIII expression of CAFs may serve as a novel target for the treatment of oral carcinoma.