RT Journal Article SR Electronic T1 Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6731 OP 6737 VO 37 IS 12 A1 KURODA, HIROMASA A1 KURIO, NAITO A1 SHIMO, TSUYOSHI A1 MATSUMOTO, KENICHI A1 MASUI, MASANORI A1 TAKABATAKE, KIYOFUMI A1 OKUI, TATSUO A1 IBARAGI, SOICHIRO A1 KUNISADA, YUKI A1 OBATA, KYOICHI A1 YOSHIOKA, NORIE A1 KISHIMOTO, KOJI A1 NAGATSUKA, HITOSHI A1 SASAKI, AKIRA YR 2017 UL http://ar.iiarjournals.org/content/37/12/6731.abstract AB 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.