The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma
The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma
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DOI：
10.3390/ijms20225779
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Nagatsuka, Hitoshi
中科院分区：
文献类型：
--
作者：
Takabatake, Kiyofumi;Shimo, Tsuyoshi;Nagatsuka, Hitoshi
已在几种人类癌症中鉴定出Sonic hedgehog（SHH）及其信号传导，并且SHH表达水平的增加似乎与癌症进展相关。然而，SHH在口腔鳞状细胞癌（OSCC）肿瘤微环境（TME）中的作用尚不清楚。目前尚没有研究比较SHH在不同亚型口腔鳞癌中的表达，也没有研究关注SHH在肿瘤实质和间质中的关系。在这项研究中，我们分析了SHH及其受体Patched-1（PTCH）在不同亚型OSCC TME中的表达。15例内生型（艾德型）和15例外生型（EX型）口腔鳞癌。对这些样品进行H&E染色、免疫组织化学（IHC）、双重IHC和双重荧光IHC。ED型薄壁组织比EX型薄壁组织更强地表达SHH和PTCH。在OSCC间质中，CD 31阳性癌血管、CD 68和CD 11b阳性巨噬细胞和α-平滑肌肌动蛋白阳性癌相关成纤维细胞部分表达PTCH。另一方面，在EX型基质中，几乎没有观察到双阳性细胞。这些结果表明SHH的自分泌作用诱导了肿瘤的侵袭，而SHH的旁分泌作用控制了口腔鳞癌的实质-间质相互作用。SHH途径的作用是促进生长和入侵。
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 alpha-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.