Main author: Anna Karen Sigurðardóttir
Institution or Company: Rannsóknastofa í stofnfrumufræðum
Co-Authors, Company or Institution:
Arna Steinunn Jónasdóttir, Rannsóknastofa í stofnfrumufræðum. Árni Ásbjarnarson, Rannsóknastofa í stofnfrumufræðum. Þórarinn Guðjónsson, Rannsóknastofa í stofnfrumufræðum. Gunnhildur Ásta Traustadóttir, Rannsóknastofa í stofnfrumufræðum.
Introduction: D492 is an epithelial cell line originally isolated from the stem cell population of the breast and generates both luminal and myoepithelial cells in culture. When D492 cells are embedded into 3D reconstituted basement membrane matrix (3D-rBM) they form branching colonies mimicking the TDLUs of the breast, thereby providing a well-suited in vitro model for studies on branching morphogenesis and breast development. Peroxidasin (PXDN) is a heme-containing peroxidase that crosslinks collagen IV with the formation of sulfilimine bonds. Although PXDN has been linked to fibrosis and cancer in some organs there is limited information on its role in development, including in the breast.
Methods: In this study, we demonstrate expression of PXDN in breast epithelium and stroma and apply the D492 cell line in monolayer and 3D-culture to investigate the role of PXDN in cell differentiation and branching morphogenesis in the human breast.
Results: Overexpression of PXDN induced basal phenotype in D492 cells, mediated through upregulation of p63, and loss of plasticity and inhibition of EMT as is displayed by complete inhibition of branching morphogenesis in 3D culture. This is supported by results from RNA-sequencing which show significant enrichment in genes involved in epithelial differentiation along with significant negative enrichment of EMT factors.
Conclusions: We provide evidence for a novel role of PXDN in breast epithelial differentiation and mammary gland development through a previously unknown relationship with the transcription factor p63.
