RRC ID 52286
著者 Takada H, Ibaragi S, Eguchi T, Okui T, Obata K, Masui M, Morisawa A, Takabatake K, Kawai H, Yoshioka N, Hassan NMM, Shimo T, Hu GF, Nagatsuka H, Sasaki A.
タイトル Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma.
ジャーナル Int J Oncol
Abstract Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.
巻・号 51(2)
ページ 625-632
公開日 2017-8-1
DOI 10.3892/ijo.2017.4050
PMID 28656278
PMC PMC8353226
MeSH Animals Antigens, CD / genetics* Bone Neoplasms / genetics* Bone Neoplasms / pathology Bone Neoplasms / secondary Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement / genetics Gene Expression Regulation, Neoplastic / genetics Head and Neck Neoplasms / genetics* Head and Neck Neoplasms / pathology Humans Insulin-Like Growth Factor I / genetics* Mice Neoplasm Invasiveness / genetics Neovascularization, Pathologic / genetics* Neovascularization, Pathologic / pathology Oligodendroglia / metabolism Osteoclasts / pathology RANK Ligand / genetics Semaphorins / genetics* Semaphorins / metabolism Squamous Cell Carcinoma of Head and Neck Xenograft Model Antitumor Assays
IF 3.899
引用数 8
リソース情報
ヒト・動物細胞 HSC-2(RCB1945) SAS(RCB1974) ST2(RCB0224)