The Expression of Selected Wnt Pathway Members (FZD6, AXIN2 and β-Catenin) in Canine Oral Squamous Cell Carcinoma and Acanthomatous Ameloblastoma.

Barbora Putnová,Marcela Buchtová,Iveta Putnová,Miša Škorič

doi:10.3390/ani11061615

Abstract

Simple SummaryThe expression patterns of selected Wnt pathway molecules were analyzed in two of the most common canine oral neoplasia—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). We found an overlap of areas with high expression of FZD6 and SOX2 in COSCC, while cytokeratin expression was low in these areas, indicating the low differentiation status of these cells. In CAA, FZD6-positive areas expressed cytokeratin and exhibited features of squamous metaplasia. Moreover, the expression of β-catenin and AXIN2 was higher in both CAA and COSCC than in the healthy canine oral epithelium. This work uncovered the distinct expression patterns of Wnt molecules in both lesions, indicating the involvement of this pathway in the pathology of canine oral cancers, which presents opportunities for their usage for the prediction of cell behavior or in the development of new therapeutic approaches.The Wnt signaling pathway is well known to be involved in many types of human cancer; however, in veterinary medicine, the investigation of individual Wnt members’ expression, and their role in or association with oral tumor pathogenesis, is still underevaluated. We aim to determine the expression pattern of Frizzled-6 (FZD6) as one of the Wnt receptors in two of the most common canine oral neoplastic lesions—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). While COSCC is a malignant tumor with aggressive biological behavior and a tendency to metastasize, CAA is a benign tumor with high local invasiveness. In CAA, the expression of FZD6 was mostly located in the center of the epithelial tumorous tissue, and cells exhibiting features of squamous metaplasia were strongly positive. In well-differentiated COSCC, FZD6 was expressed in the tumorous epithelium as well as the tumorous stroma. There was a negative correlation between cytokeratin expression and FZD6 expression in COSCC, where the central parts of the epithelial tumorous tissue were often FZD6-negative. The non-differentiated COSCC with low expression of cytokeratin exhibited a diffuse FZD6 signal. The invasive front with areas of tumor budding exhibited high FZD6 expression with a loss of cytokeratin expression. Moreover, the expression of β-catenin and AXIN2 was increased in comparison to gingiva. In conclusion, our study revealed significant differences in the expression patterns and the levels of FZD6 between COSCC and CAA, indicating the differential engagement of the Wnt pathway in these tumors.

Highlights

With the rapid developments in the field of veterinary oncology, there is an increasing need for a deeper understanding of the molecular regulations of animal cancer development
Canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA) exhibit distinct morphological features and the diagnosis is usually performed based on common histological staining
Because β-catenin is translocated to the nucleus in the “wingless-related integration site pathway (Wnt)-on” state [66], we suggest that the well-differentiated cells in COSCC are those where Wnt signaling is activated, whereas in the less differentiated Sex determining region Y box 2 (SOX2)-positive cells, the Wnt signaling is disrupted, which might lead to the aggressive behavior of these cells

Summary

Introduction

With the rapid developments in the field of veterinary oncology, there is an increasing need for a deeper understanding of the molecular regulations of animal cancer development. We focus on two of the most common canine oral tumors of epithelial origin: oral squamous cell carcinoma and acanthomatous ameloblastoma [2]. Canine oral squamous cell carcinoma (COSCC) is the second most common malignancy in the oral cavity of dogs. They usually form ulcerated masses and plaques on the tongue or buccal mucosa [3]. These lesions invade the surrounding structures, but the prognosis is auspicious after radical chirurgical excision at early stages [4]. The pathogenesis of this neoplasia is not yet fully understood, canine OSCC is considered to be a possible model for a human OSCC [8]

Objectives

Methods

Results

Discussion

Conclusion