TY - JOUR
T1 - The role of sonic hedgehog signaling in the tumor microenvironment of oral squamous cell carcinoma
AU - Takabatake, Kiyofumi
AU - Shimo, Tsuyoshi
AU - Murakami, Jun
AU - Anqi, Chang
AU - Kawai, Hotaka
AU - Yoshida, Saori
AU - Oo, May Wathone
AU - Haruka, Omori
AU - Sukegawa, Shintaro
AU - Tsujigiwa, Hidetsugu
AU - Nakano, Keisuke
AU - Nagatsuka, Hitoshi
N1 - Funding Information:
Funding: This study was jointly funded by the Japan Society for Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (16K11722, 18K09789, 18K17224, 19K19159, 19K24094 and 19K19160).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/11/2
Y1 - 2019/11/2
N2 - 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.
AB - 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.
KW - Cancer-associated fibroblasts (CAFs)
KW - Oral squamous cell carcinoma (OSCC)
KW - Sonic hedgehog (SHH)
KW - Tumor microenvironment (TME)
KW - Tumor-associated angiogenesis
KW - Tumor-associated macrophages (TAMs)
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U2 - 10.3390/ijms20225779
DO - 10.3390/ijms20225779
M3 - Article
C2 - 31744214
AN - SCOPUS:85075218120
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 22
M1 - 5779
ER -
