Fibulin-2 is required for basement membrane integrity of mammary epithelium

Scientific Reports
Ayman M IbrahimT Stein

Abstract

Fibulin-2 (FBLN2) is a secreted extracellular matrix glycoprotein which has been associated with tissue development and remodelling. In the mouse mammary gland, FBLN2 can be detected during ductal morphogenesis in cap cells and myoepithelial cells at puberty and early pregnancy, respectively. In an attempt to assign its function, we knocked down Fbln2 in the mouse mammary epithelial cell line EpH4. FBLN2 reduction led to an increase in the size of spheroidal structures when compared to scrambled control shRNA-transduced cells plated on Matrigel matrix. This phenotype was associated with a disruption of the collagen IV sheath around the epithelial spheroids and downregulation of integrin β1, suggesting a role for FBLN2 in stabilizing the basement membrane (BM). In contrast to mice, in normal adult human breast tissue, FBLN2 was detected in ductal stroma, and in the interlobular stroma, but was not detectable within the lobular regions. In tissue sections of 65 breast cancers FBLN2 staining was lost around malignant cells with retained staining in the neighbouring histologically normal tissue margins. These results are consistent with a role of FBLN2 in mammary epithelial BM stability, and that its down-regulation in breast cance...Continue Reading

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Citations

May 1, 2020·NPJ Precision Oncology·Ayman M IbrahimHeather L Machado
Oct 3, 2020·International Journal of Molecular Sciences·Ayman M IbrahimMagdi Yacoub
Dec 3, 2020·PloS One·Lee D TroughtonKevin J Hamill
Feb 18, 2021·NPJ Precision Oncology·Ayman M IbrahimHeather L Machado
Dec 12, 2020·Arthritis & Rheumatology·Jessica L TurnierJ Michelle Kahlenberg

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Methods Mentioned

BETA
PCR
Phase
transfection
Protein Assay

Software Mentioned

3000
FACSDiva
CellP Imaging
ImageJ
LAS

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