Canine Epithelial Skin Tumours: Expression of the Stem Cell Markers Lgr5, Lgr6 and Sox9 in Light of New Cancer Stem Cell Theories.

Laura Bongiovanni,Eva Moreno,Chiara Brachelente,Monika M Welle

doi:10.3390/vetsci7020062

Laura Bongiovanni, Eva Moreno + Show 2 more

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https://doi.org/10.3390/vetsci7020062

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Abstract

Evidence is accumulating that tumour development is driven by cancer stem cells (CSCs). In order to understand the presence and potential contribution of stem cells (SCs) as tumour-initiating cells in canine cutaneous tumours, we selected three putative SC markers (Lgr5, Lgr6 and Sox9) and investigated their expression pattern, level of protein and mRNA expression, in 43 canine hair follicle (HF) and 18 canine cutaneous epidermal tumours by immunohistochemistry and qRT-PCR, using normal skin samples as controls. Lgr5 protein expression was not detected in epidermal and HF tumours; however, Lgr5 mRNA overexpression was evident in some HF tumours. Sox9 was expressed in several tumour cases, both at the protein and mRNA level. The Lgr6 antibody tested was not suitable for formalin-fixed paraffin-embedded tissue samples, but Lgr6 gene showed higher expression in several samples of both HF and epidermal tumours compared with normal skin. Significantly higher mRNA expression levels of the three SC markers were found in trichoblastomas (TB) compared with basal cell carcinomas (BCC). The present results indicated that canine HF and epidermal tumours might have common tumour-initiating cells. The mRNA expression of the three selected SC markers, especially Lgr5, could be potentially useful in the distinction between canine TB and BCC.

Highlights

A hierarchical organization of tumour cells has been proposed for most of the tumour types, based on the existence of a specific population of tumour-initiating cells (TICs) with unlimited capacity for self-renewal and proliferation
Based on our experiments and on the fact that the same antibody was previously confirmed to work on fresh canine normal skin samples by western blot [11], we concluded that the applied anti-Lgr6 antibody was not working on formalin-fixed paraffin-embedded tissue samples
It has been shown in mice, that Lgr6 protein expression is located in the stem cell niche above the bulge; this protein is considered as a marker of hair follicle (HF) stem cells that are able to give rise to all lineages of the skin (HF, sebaceous gland and interfollicular epidermis), and to contribute to wound healing

Summary

Introduction

A hierarchical organization of tumour cells has been proposed for most of the tumour types, based on the existence of a specific population of tumour-initiating cells (TICs) with unlimited capacity for self-renewal and proliferation. In the so-called TIC model, a specific neoplastic cell population exhibits stem cell characteristics, having the ability to generate both, differentiated, highly proliferative tumour cells as well as other self-renewing TICs that can regenerate all tumour cell types [1]. The term TICs is often used interchangeably with “cancer stem cells” (CSCs). A new concept has emerged in the last years about the active role of the stem cell niche in regulating the hierarchical organization of tumour cells. Cells that remain within the niche are stem cells, while those that

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