RRC ID 67528
Author Nakamura R, Kayamori K, Oue E, Sakamoto K, Harada K, Yamaguchi A.
Title Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma.
Journal Biochem Biophys Res Commun
Abstract Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction.
Volume 458(4)
Pages 777-82
Published 2015-3-20
DOI 10.1016/j.bbrc.2015.02.013
PII S0006-291X(15)00227-2
PMID 25681764
MeSH Animals Bone Resorption / complications* Bone Resorption / metabolism Bone Resorption / pathology Carcinoma, Squamous Cell / complications* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Line Cell Line, Tumor Humans Mice Mouth Neoplasms / complications* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Osteoclasts / metabolism Osteoclasts / pathology RANK Ligand Smad2 Protein / metabolism Stromal Cells / metabolism* Stromal Cells / pathology Transforming Growth Factor beta / metabolism*
IF 2.985
Human and Animal Cells RAW 264(RCB0535) ST2(RCB0224)