Activated Hair Follicle Stem Cells and Wnt/β-catenin Signaling Involve in Pathnogenesis of Sebaceous Neoplasms

Abstract

Sebaceous glands (SGs) undergo cyclic renewal independent of hair follicle stem cells (HFSCs) activation while HFSCs have the potential to differentiate into sebaceous gland cells, hair follicle and epidermal keratinocytes. Abnormalities of sebaceous gland progenitor cells contribute to the development of sebaceous neoplasms, but little is known about the role of HFSCs during sebaceous neoplasm development. Here, using dimethylbenzanthracene (DMBA) plus 12-o-tetradecanoyl phorbol-13-acetate (TPA) treatment developing sebaceous neoplasms (SNs) were identified with H&E and Oil red O staining. And then the molecular expression and activation of HFSCs and was characterized by immunostaining. Wnt10b/β-catenin signaling molecular which is important for activation of HFSCs were detected by immunostaining. We found hair follicle and epidermal cell markers were expressed in sebaceous neoplasms. Furthermore, SOX-9 and CD34-positive HFSCs were located in the basal layer of sebaceous lobules within the sebaceous neoplasms. Many appear to be in an active state. Finally, Wnt10b/β-catenin signaling was activated within the basal cells of sebaceous lobules in the sebaceous neoplasms. Collectively, our findings suggest that the abnormal activation of both HFSCs and Wnt10b/β-catenin signaling involves in the development of sebaceous neoplasms.

Wnt/β-catenin signaling promotes aging-associated hair graying in mice

“…Wnt signaling usually maintains at a low level which is under the threshold for hair follicle stem cell activation at telogen [ 29 ]. Overexpression of β-catenin in epidermis induces ectopic hair follicle regeneration [ 30 ], and even tumorigenesis [ 31 ]. In our study, we found β-catenin expression is increased in telogen skin of aged mice compared to those in young mice.…”

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28

“…Furthermore, hair follicle tumors were observed to have stable expression of β-catenin in mice (Gat et al, 1998). A recent study found hair follicle stem cells (HFSC) treated with dimethylbenzanthracene (DMBA) and 12- O -Tetradecanoylphorbol-13-acetate (TPA) induced sebaceous neoplasms in C57BL/6 mice, as well as increased Wnt10b expression in basal cells via immunostaining (Qiu et al, 2014). Here the authors propose a model wherein increased Wnt10b results in proliferation and differentiation of HFSCs and thus promoting sebaceous neoplasms.…”

Expression of epidermal stem cell markers in skin and adnexal malignancies

“…Other neoplasms of skin appendages, such as neoplasms of eccrine or sebaceous glands, have only been examined in a few cases. Human sebaceous neoplasms, especially sebaceoma, and also sebaceous carcinomas, have been reported to express CK15, SOX9 and β‐catenin, as have mouse models of sebaceous neoplasms . CK15, CK19, carcinoembryonic antigen, CAM5·2 and nestin have been reported to stain poroma and porocarcinoma to enable distinction from SCCs …”

“…Human sebaceous neoplasms, especially sebaceoma, and also sebaceous carcinomas, have been reported to express CK15, SOX9 and b-catenin, 25,30,41 as have mouse models of sebaceous neoplasms. 41,42 CK15, CK19, carcinoembryonic antigen, CAM5Á2 and nestin have been reported to stain poroma and porocarcinoma to enable distinction from SCCs. 43,44 We used markers that had been previously reported, such as CK15, b-catenin and SOX9, together with hair follicle stem cell markers that have not been previously reported, such as Lgr5 [except for the detection of Lgr5 (GPR49) mRNA in BCCs] 45 and Lrig1, but that label different areas of the hair follicle to enact a cell origin profile in skin appendage malignancies.…”