The role of sonic hedgehog signaling in the tumor microenvironment of oral squamous cell carcinoma

Kiyofumi Takabatake, Tsuyoshi Shimo, Jun Murakami, Chang Anqi, Hotaka Kawai, Saori Yoshida, May Wathone Oo, Omori Haruka, Shintaro Sukegawa, Hidetsugu Tsujigiwa, Keisuke Nakano, Hitoshi Nagatsuka

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5779
JournalInternational journal of molecular sciences
Volume20
Issue number22
DOIs
Publication statusPublished - Nov 2 2019

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Tumor Microenvironment
Tumors
Squamous Cell Carcinoma
tumors
cancer
Immunohistochemistry
Neoplasms
Macrophages
Blood vessels
Fibroblasts
Smooth Muscle
Blood Vessels
Muscle
Epithelial Cells
Actins
Cells
smooth muscle
Staining and Labeling
macrophages
blood vessels

Keywords

  • Cancer-associated fibroblasts (CAFs)
  • Oral squamous cell carcinoma (OSCC)
  • Sonic hedgehog (SHH)
  • Tumor microenvironment (TME)
  • Tumor-associated angiogenesis
  • Tumor-associated macrophages (TAMs)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

The role of sonic hedgehog signaling in the tumor microenvironment of oral squamous cell carcinoma. / Takabatake, Kiyofumi; Shimo, Tsuyoshi; Murakami, Jun; Anqi, Chang; Kawai, Hotaka; Yoshida, Saori; Oo, May Wathone; Haruka, Omori; Sukegawa, Shintaro; Tsujigiwa, Hidetsugu; Nakano, Keisuke; Nagatsuka, Hitoshi.

In: International journal of molecular sciences, Vol. 20, No. 22, 5779, 02.11.2019.

Research output: Contribution to journalArticle

Takabatake, Kiyofumi ; Shimo, Tsuyoshi ; Murakami, Jun ; Anqi, Chang ; Kawai, Hotaka ; Yoshida, Saori ; Oo, May Wathone ; Haruka, Omori ; Sukegawa, Shintaro ; Tsujigiwa, Hidetsugu ; Nakano, Keisuke ; Nagatsuka, Hitoshi. / The role of sonic hedgehog signaling in the tumor microenvironment of oral squamous cell carcinoma. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 22.
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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.",
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