Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis.
Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis.
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DOI：
10.21873/anticanres.12132
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发表时间：
2017-12
影响因子：
2
通讯作者：
Hiromasa Kuroda;N. Kurio;T. Shimo;Kenichi Matsumoto;M. Masui;Kiyofumi Takabatake;T. Okui;S. Ibaragi;Y. Kunisada;K. Obata;Norie Yoshioka;K. Kishimoto;H. Nagatsuka;A. Sasaki
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文献类型：
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作者：
Hiromasa Kuroda;N. Kurio;T. Shimo;Kenichi Matsumoto;M. Masui;Kiyofumi Takabatake;T. Okui;S. Ibaragi;Y. Kunisada;K. Obata;Norie Yoshioka;K. Kishimoto;H. Nagatsuka;A. Sasaki
研究背景声刺猬信号与口腔鳞状细胞癌的发病机制有关，但其在口腔鳞状细胞癌中的作用尚不清楚。在这项研究中，我们分析了SHH信号在OSCC中的作用。材料与方法：采用免疫组织化学方法检测SHH及其信号蛋白在临床切除的口腔鳞癌标本中的表达。我们还使用hedgehog信号传导抑制剂cyclopamine在体内和体外通过增殖、迁移和血管生成分析来评估SHH信号传导的功能。结果SHH在人舌OSCC中高表达，而Patched（PTCH 1）、胶质瘤相关癌基因1（GLI1）和GLI2蛋白在肿瘤浸润前沿的微血管细胞中表达。给予小鼠环巴胺抑制了体内OSCC异种移植物的生长和血管生成。此外，环巴胺抑制内皮细胞增殖和迁移，并减少大鼠主动脉血管长度。结论OSCC源性SHH可促进肿瘤浸润前沿的血管生成。
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.