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.
Highlights
Oral squamous cell carcinoma (OSCC) is a malignant tumor that comprises up to 90% of tumors in the head and neck region [1] and is a heterogeneous group of tumors arising from the mucosal surfaces of the oral cavity.oral squamous cell carcinoma (OSCC) is classified into various subtypes as described in the World Health Organization (WHO) Classification of Head and Neck Tumors 4th Ed [2]
To investigate how the expression of sonic hedgehog (SHH) and its receptor PTCH influence on the invasion of OSCC, we examined the expression of SHH and PTCH in the parenchymal and stromal regions comparing ED-type and EX-type specimens
The role of SHH in OSCC tumor microenvironment (TME) was clarified by comparing the expression of SHH by endophytic-type cases (ED type) and exophytic-type cases (EX type) by immunostaining
Summary
OSCC is classified into various subtypes as described in the World Health Organization (WHO) Classification of Head and Neck Tumors 4th Ed [2]. Macroscopic subtypes have been identified, based on the clinical invasion pattern. These subtypes have important differences in prognosis due to differences in invasive ability. The stroma of the TME is composed of multiple different cell types, such as macrophages, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. These subpopulations of cells interact with each other as well as with cancer cells via complex communication networks through various secreted cytokines, chemokines, growth factors, and proteins of the extracellular matrix
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