Main author: Arna Steinunn Jónasdóttir
Institution or Company: Lífvísindasetur Háskóla Íslands
Co-Authors, Institution or Company:
Anna Karen Sigurðardóttir, Lífvísindasetur Háskóla Íslands. Árni Ásbjarnarson, Lífvísindasetur Háskóla Íslands. Þórarinn Guðjónsson, Lífvísindasetur Háskóla Íslands. Gunnhildur Ásta Traustadóttir, Lífvísindasetur Háskóla Íslands.
Introduction: Peroxidasin (PXDN) is a secreted enzyme that catalyzes crosslinking of Collagen IV in the basement membrane (BM). PXDN is highly important for normal development but has also been linked to epithelial to mesenchymal transition (EMT) and fibrosis. Moreover, PXDN is associated with cancer progression in melanoma and ovarian cancer. Nevertheless, little is known about the role of PXDN in normal and neoplastic mammary gland. Previous research from our laboratory links PXDNs role to EMT and mesenchymal to epithelial transition (MET) in branching morphogenesis in the mammary gland. Given that EMT and MET are utilized by cancer cells for mobility in metastasis we hypothesize that PXDN may play a role in breast cancer progression.
Methods: Cell culture, 3D models, Lentiviral transfection, migration, invasion, apoptosis, qPCR, Western Blot and IF staining. Data mining in publicly available database (BreastMark).
Results: Data collected from BreastMark show that high expression of PXDN in HER2+ breast cancer subtypes is linked to poor survival, higher likelihood of metastasis and a larger primary tumor at diagnosis. To study the role of PXDN on cellular level, PXDN was overexpressed in SKBR3 (HER2+) and HCC1143 (Triple-negative) breast cancer cell lines. In the HER2+ cell line (SKBR3), PXDN overexpression increased invasion and resistance to CP724714, a small molecular inhibitor of HER2 receptor. Increased PXDN levels in the triple negative cell line (HCC1143) resulted in reduced proliferation and decreased invasion.
Conclusion: Taken together, overexpression of PXDN in breast cancer cell lines seems to induce a more aggressive phenotype with increased invasion.
