Hiromasa Kuroda1, Naito Kurio1,2, Tsuyoshi Shimo3, Kenichi Matsumoto1, Masanori Masui1, Kiyofumi Takabatake4, Tatsuo Okui1, Soichiro Ibaragi1, Yuki Kunisada1, Kyoichi Obata1, Norie Yoshioka1, Koji Kishimoto1, Hitoshi Nagatsuka4, Akira Sasaki1. 1. Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 2. Department of Oral Surgery, Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Institute of Health Biosciences, Graduate School of Tokushima University, Tokushima, Japan. 3. Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan shimotsu@md.okayama-u.ac.jp. 4. Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Abstract
BACKGROUND: Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood. In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND METHODS: We examined the expression pattern of SHH and its signal proteins in clinically resected OSCC samples by immunohistochemistry. We also evaluated the function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in vivo and in vitro by proliferation, migration and angiogenesis analyses. RESULTS: We found that SHH was highly expressed in human tongue OSCC, whereas patched (PTCH1), glioma-associated oncogene 1 (GLI1) and GLI2 proteins were expressed in the microvascular cells in the tumor invasive front. Administration of cyclopamine to mice suppressed the growth and angiogenesis of OSCC xenografts in vivo. Moreover, cyclopamine inhibited endothelial cell proliferation and migration, and reduced aorta vascular length in the rat. CONCLUSION: These findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor invasive front. Copyright
BACKGROUND:Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood. In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND METHODS: We examined the expression pattern of SHH and its signal proteins in clinically resected OSCC samples by immunohistochemistry. We also evaluated the function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in vivo and in vitro by proliferation, migration and angiogenesis analyses. RESULTS: We found that SHH was highly expressed in human tongue OSCC, whereas patched (PTCH1), glioma-associated oncogene 1 (GLI1) and GLI2 proteins were expressed in the microvascular cells in the tumor invasive front. Administration of cyclopamine to mice suppressed the growth and angiogenesis of OSCC xenografts in vivo. Moreover, cyclopamine inhibited endothelial cell proliferation and migration, and reduced aorta vascular length in the rat. CONCLUSION: These findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor invasive front. Copyright
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