Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma

Takada,Hiroyuki; Ibaragi,Soichiro; Eguchi,Takanori; Okui,Tatsuo; Obata,Kyoichi; Masui,Masanori; Morisawa,Ayaka; Takabatake,Kiyofumi; Kawai,Hotaka; Yoshioka,Norie; Hassan,Nur Mohammad Monsur; Shimo,Tsuyoshi; Hu,Guo-Fu; Nagatsuka,Hitoshi; Sasaki,Akira

doi:10.3892/ijo.2017.4050

Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma

Authors:
- Hiroyuki Takada
- Soichiro Ibaragi
- Takanori Eguchi
- Tatsuo Okui
- Kyoichi Obata
- Masanori Masui
- Ayaka Morisawa
- Kiyofumi Takabatake
- Hotaka Kawai
- Norie Yoshioka
- Nur Mohammad Monsur Hassan
- Tsuyoshi Shimo
- Guo-Fu Hu
- Hitoshi Nagatsuka
- Akira Sasaki
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Affiliations: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama, Japan, Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama, Japan, Departments of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama, Japan, School of Dentistry and Health Sciences, Charles Sturt University, Orange NSW, Australia, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA
Published online on: June 21, 2017 https://doi.org/10.3892/ijo.2017.4050
Pages: 625-632

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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.

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