TY - JOUR
T1 - Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis
AU - Kuroda, Hiromasa
AU - Kurio, Naito
AU - Shimo, Tsuyoshi
AU - Matsumoto, Kenichi
AU - Masui, Masanori
AU - Takabatake, Kiyofumi
AU - Okui, Tatsuo
AU - Ibaragi, Soichiro
AU - Kunisada, Yuki
AU - Obata, Kyoichi
AU - Yoshioka, Norie
AU - Kishimoto, Koji
AU - Nagatsuka, Hitoshi
AU - Sasaki, Akira
N1 - Publisher Copyright:
© 2017 International Institute of Anticancer Research. All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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.
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.
KW - Angiogenesis
KW - Oral squamous cell carcinoma
KW - Sonic hedgehog signaling
KW - Tongue
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U2 - 10.21873/anticanres.12132
DO - 10.21873/anticanres.12132
M3 - Article
C2 - 29187450
AN - SCOPUS:85038367245
SN - 0250-7005
VL - 37
SP - 6731
EP - 6737
JO - Anticancer Research
JF - Anticancer Research
IS - 12
ER -
