Official websites use. Share sensitive information only on official, secure websites. However, the related regulatory mechanisms are not completely understood. In this study, we examined the role of heparan sulfate HS in PrSC self-renewal and prostate regeneration. Using an in vitro prostate sphere formation assay, we found that deletion of the glycosyltransferase exostosin 1 Ext1 abolished HS expression in PrSCs and disrupted their ability to self-renew.
Mechanistically, HS expressed by PrSCs in cis or by neighboring cells in trans could maintain sphere formation. In an in vivo prostate regeneration assay, simultaneous loss of HS in both epithelial cell and stromal cell compartments attenuated prostate tissue regeneration, whereas the retention of HS expression in either of the two cellular compartments was sufficient to sustain prostate tissue regeneration.
The prostate is a complex tubuloalveolar exocrine gland of the male reproductive system in mammals. The gland contains two major epithelial cell types: secretory luminal cells, which contribute to the bulk of seminal fluid, and basal cells that line the basement membrane Wang et al. A small population of neuroendocrine cells also exists within the basal cell layer and regulates the activity of the two aforementioned epithelial lineages Aumuller et al.
The prostate epithelial cells PrECs are in an intimate contact with the surrounding stroma, which includes fibroblasts, smooth muscle, nerves and lymphatics. Interactions between the stromal and the epithelial compartment have been shown to mediate multiple growth factor signaling pathways that are involved not only in the growth and development of the prostate but also in the prostate cancer Josson et al. The adult prostate is capable of undergoing multiple cycles of atrophy and regeneration following castration and readministration of androgen.
Intensive investigations have been taken to delineate the molecular mechanisms that regulate PrSCs fate determination. In this regards, some achievements have been made Strand and Goldstein Heparan sulfate HS is a linear anionic polysaccharide expressed ubiquitously on the cell surface and in extracellular matrix ECM , where it is covalently linked to core proteins to form HS proteoglycans Wang et al.
