Fibulin-2 is involved in early extracellular matrix development of the outgrowing mouse mammary epithelium

• Published in: Cellular and molecular life sciences : CMLS Vol. 71; no. 19; pp. 3811 - 3828
• Main Authors: Olijnyk, D, Ibrahim, A. M, Ferrier, R. K, Tsuda, T, Chu, M.-L, Gusterson, B. A, Stein, T, Morris, J. S
• Format: Journal Article
• Language: English
• Published: Basel Springer-Verlag 01-10-2014; Springer Basel; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Calcium-Binding Proteins - deficiency; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; cell adhesion; Cell adhesion & migration; Cell Biology; Cell Movement - drug effects; Cells, Cultured; Cellular biology; epithelium; Estrogens; Estrogens - pharmacology; extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - deficiency; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; fibronectins; Fibronectins - metabolism; gene expression; hormonal regulation; knockout mutants; laminin; Laminin - analysis; Laminin - metabolism; Life Sciences; Male; mammary glands; Mammary Glands, Animal - cytology; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - metabolism; messenger RNA; Mice; Mice, Inbred C57BL; Mice, Knockout; muscle development; phenotype; Pregnancy; progesterone; Progesterone - pharmacology; Proteins; proteoglycans; puberty; Research Article; RNA, Messenger - metabolism; smooth muscle; Versicans - analysis; Versicans - metabolism; Terminal end buds; Epithelial-stromal interactions; Mammary gland; Fibulin-2; Versican
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-014-1577-4

Cell–matrix interactions control outgrowth of mammary epithelium during puberty and pregnancy. We demonstrate here that the glycoprotein fibulin-2 (FBLN2) is strongly associated with pubertal and early pregnant mouse mammary epithelial outgrowth. FBLN2 was specifically localized to the cap cells of the terminal end buds during puberty and to myoepithelial cells during very early pregnancy (days 2–3) even before morphological changes to the epithelium become microscopically visible, but was down-regulated thereafter. Exposure to exogenous oestrogen (E2) or E2 plus progesterone (P) increased Fbln2 mRNA expression in the pubertal gland, indicating hormonal control. FBLN2 was co-expressed and co-localised with the proteoglycan versican (VCAN) and co-localised with laminin (LN), while over-expression of FBLN2 in HC-11 cells increased cell adhesion to several extracellular matrix proteins including LN and fibronectin, but not collagens. Mammary glands from Fbln2 knockout mice showed no obvious phenotype but increased fibulin-1 (FBLN1) staining was detected, suggesting a compensatory mechanism by other fibulin family members. We hypothesise that similar to embryonic aortic smooth muscle development, FBLN2 and VCAN expression alters the cell–matrix interaction to allow mammary ductal outgrowth and development during puberty and to enable epithelial budding during pregnancy.