M Ibrahim, AymanSabet, SalwaA El-Ghor, AkmalKamel, NoraE Anis, ShadyS Morris, JoannaStein, Torsten2020-02-102020-02-1020181. Ghoncheh, M., Pournamdar, Z. & Salehiniya, H. Incidence and Mortality and Epidemiology of Breast Cancer in the World. Asian Pac. J. Cancer Prev. 17, 43–46 (2016). Article PubMed Central Google Scholar 2. Miller, K. D. et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66, 271–289, https://doi.org/10.3322/caac.21349 (2016). Article Google Scholar 3. Cichon, M. A., Degnim, A. C., Visscher, D. W. & Radisky, D. C. Microenvironmental influences that drive progression from benign breast disease to invasive breast cancer. Journal of Mammary Gland Biology and Neoplasia 15, 389–397, https://doi.org/10.1007/s10911-010-9195-8 (2010). Article PubMed PubMed Central Google Scholar 4. Bissell, M. J., Kenny, P. A. & Radisky, D. C. Microenvironmental regulators of tissue structure and function also regulate tumor induction and progression: the role of extracellular matrix and its degrading enzymes. Cold Spring Harb. Symp. Quant. Biol. 70, 343–356, https://doi.org/10.1101/sqb.2005.70.013 (2005). CAS Article PubMed PubMed Central Google Scholar 5. Insua-Rodríguez, J. & Oskarsson, T. The extracellular matrix in breast cancer. Adv. Drug Deliv. Rev. 97, 41–55, https://doi.org/10.1016/j.addr.2015.12.017 (2016). CAS Article PubMed PubMed Central Google Scholar 6. Lu, P., Weaver, V. M. & Werb, Z. The extracellular matrix: a dynamic niche in cancer progression. J. Cell Biol. 196, 395–406, https://doi.org/10.1083/jcb.201102147 (2012). CAS Article PubMed PubMed Central Google Scholar 7. Zhang, H. Y., Timpl, R., Sasaki, T., Chu, M. L. & Ekblom, P. Fibulin-1 and fibulin-2 expression during organogenesis in the developing mouse embryo. Dev. Dyn. 205, 348–364, https://doi.org/10.1002/(sici)1097-0177(199603)205:33482045-2322 (online)https://t.ly/j7W9DMSA Google ScholarFibulin-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.enBreast cancerCellular imagingMechanisms of diseaseArticle