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Volume 20
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10.3390/ijms20225779
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Article

The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma

by
Kiyofumi Takabatake
1,*,
Tsuyoshi Shimo
2,
Jun Murakami
3,
Chang Anqi
1,4,
Hotaka Kawai
1,
Saori Yoshida
1,
May Wathone Oo
1,
Omori Haruka
1,
Shintaro Sukegawa
1,5,
Hidetsugu Tsujigiwa
1,6,
Keisuke Nakano
1 and
Hitoshi Nagatsuka
1
1
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 7008525, Japan
2
Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 0610293, Japan
3
Department of Oral and Maxillofacial Radiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 7008525, Japan
4
Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin 150081, China
5
Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, Kagawa 7608557, Japan
6
Department of Life Science, Faculty of Science, Okayama University of Science, Okayama 7000005, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5779; https://doi.org/10.3390/ijms20225779
Received: 30 October 2019 / Revised: 11 November 2019 / Accepted: 15 November 2019 / Published: 17 November 2019
(This article belongs to the Special Issue Hedgehog Signaling in Organogenesis and Tumor Microenvironment)
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Abstract

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and α-smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion. View Full-Text
Keywords: sonic hedgehog (SHH); oral squamous cell carcinoma (OSCC); tumor microenvironment (TME); tumor-associated macrophages (TAMs); cancer-associated fibroblasts (CAFs); tumor-associated angiogenesis sonic hedgehog (SHH); oral squamous cell carcinoma (OSCC); tumor microenvironment (TME); tumor-associated macrophages (TAMs); cancer-associated fibroblasts (CAFs); tumor-associated angiogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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MDPI and ACS Style

Takabatake, K.; Shimo, T.; Murakami, J.; Anqi, C.; Kawai, H.; Yoshida, S.; Wathone Oo, M.; Haruka, O.; Sukegawa, S.; Tsujigiwa, H.; Nakano, K.; Nagatsuka, H. The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2019, 20, 5779. https://doi.org/10.3390/ijms20225779

AMA Style

Takabatake K, Shimo T, Murakami J, Anqi C, Kawai H, Yoshida S, Wathone Oo M, Haruka O, Sukegawa S, Tsujigiwa H, Nakano K, Nagatsuka H. The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2019; 20(22):5779. https://doi.org/10.3390/ijms20225779

Chicago/Turabian Style

Takabatake, Kiyofumi, Tsuyoshi Shimo, Jun Murakami, Chang Anqi, Hotaka Kawai, Saori Yoshida, May Wathone Oo, Omori Haruka, Shintaro Sukegawa, Hidetsugu Tsujigiwa, Keisuke Nakano, and Hitoshi Nagatsuka. 2019. "The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma" International Journal of Molecular Sciences 20, no. 22: 5779. https://doi.org/10.3390/ijms20225779

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