Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis

Hiromasa Kuroda, Naito Kurio, Tsuyoshi Shimo, Kenichi Matsumoto, Masanori Masui, Kiyofumi Takabatake, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Norie Yoshioka, Koji Kishimoto, Hitoshi Nagatsuka, Akira Sasaki

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)6731-6737
Number of pages7
JournalAnticancer research
Issue number12
Publication statusPublished - 2017


  • Angiogenesis
  • Oral squamous cell carcinoma
  • Sonic hedgehog signaling
  • Tongue

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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