Fibulin-2 is required for basement membrane integrity of mammary epithelium
Autor: | Ayman M. Ibrahim, Salwa Sabet, Akmal A. El-Ghor, Shady E. Anis, Torsten Stein, Nora N. Kamel, Joanna S. Morris |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Collagen Type IV
0301 basic medicine lcsh:Medicine Down-Regulation Breast Neoplasms Matrix (biology) Article Basement Membrane Cell Line Mice 03 medical and health sciences Mammary Glands Animal 0302 clinical medicine Stroma medicine Animals Humans lcsh:Science Basement membrane Extracellular Matrix Proteins Matrigel Multidisciplinary Chemistry Integrin beta1 lcsh:R Calcium-Binding Proteins Myoepithelial cell Epithelial Cells Epithelium Fibulin Cell biology 030104 developmental biology medicine.anatomical_structure Mammary Epithelium Gene Knockdown Techniques 030220 oncology & carcinogenesis lcsh:Q Female |
Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
ISSN: | 2045-2322 |
Popis: | 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 cancer is associated with loss of the BM and early invasion. |
Databáze: | OpenAIRE |
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