Kuroda Hiromasa, Kurio Naito, Shimo Tsuyoshi, Matsumoto Kenichi, Masui Masanori, Takabatake Kiyofumi, Okui Tatsuo, Ibaragi Soichiro, Kunisada Yuki, Obata Kyoichi, Yoshioka Norie, Kishimoto Koji, Nagatsuka Hitoshi, Sasaki Akira
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
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.
Anticancer Res. 2017 Dec;37(12):6731-6737. doi: 10.21873/anticanres.12132.
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.
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.
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.
These findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor invasive front.
音猬因子（SHH）信号通路与口腔鳞状细胞癌（OSCC）的发病机制相关，但其在OSCC中的作用尚未完全明确。在本研究中，我们分析了SHH信号通路在OSCC中的作用。
我们通过免疫组织化学检测了临床切除的OSCC样本中SHH及其信号蛋白的表达模式。我们还通过增殖、迁移和血管生成分析，在体内和体外使用刺猬信号通路抑制剂环杷明评估了SHH信号通路的功能。
我们发现SHH在人舌OSCC中高表达，而patched（PTCH1）、胶质瘤相关癌基因1（GLI1）和GLI2蛋白在肿瘤侵袭前沿的微血管细胞中表达。给小鼠施用环杷明可抑制体内OSCC异种移植瘤的生长和血管生成。此外，环杷明抑制内皮细胞增殖和迁移，并减少大鼠主动脉血管长度。
这些发现表明，OSCC来源的SHH在肿瘤侵袭前沿刺激血管生成。
