Mammary Branching Morphogenesis Requires Reciprocal Signaling by Heparanase and MMP-14

Journal of Cellular Biochemistry
Angélica Maciel GomesM J Bissell

Abstract

The development of the mammary gland involves formation of a branched arboreal structure resulting from the penetration and proliferation of epithelial cells into the fat pad. The mammary cells invade by remodeling their surrounding extracellular matrix (ECM), which are rich in proteins, and glycans such as heparan sulfate proteoglycans (HSPGs). There is increasing literature on how the interaction between signaling by ECM and matrix metalloproteinases (MMPs) is relevant to morphogenetic and physiological contexts. Here we sought to understand how heparanase, the sole mammalian heparan sulfate-degrading endoglycosidase may regulate mammary gland development. We found a robust localization of heparanase within growing end buds during branching in vivo. Using three-dimensional (3D) organotypic cultures, we showed that heparanase expression and activity are required for mammary epithelial invasion/branching within dense collagen I gels. Morphometric analysis of glands from both heparanase-overexpressing and knockout mice showed a direct correlation between degree of branching and the heparanase levels, confirming our 3D organotypic culture observations. Finally, we uncovered a reciprocal association between levels of heparanase an...Continue Reading

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Citations

Jan 9, 2016·Advanced Drug Delivery Reviews·Jacob Insua-Rodríguez, Thordur Oskarsson
Sep 10, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Vaishali N PatelMatthew P Hoffman
Feb 15, 2017·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Marek KaweckiAleksandra Kasperczyk
Jan 18, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Guilherme Oliveira BarbosaHernandes F Carvalho
Aug 14, 2020·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Kieran M Short, Ian M Smyth
Feb 9, 2017·Journal of Mammary Gland Biology and Neoplasia·Ingrid S Paine, Michael T Lewis
Mar 30, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·James W Spurlin, Celeste M Nelson
Dec 19, 2019·Frontiers in Oncology·Deirdre R Coombe, Neha S Gandhi
Jun 15, 2020·Current Opinion in Cell Biology·Vasudha SrivastavaZev J Gartner

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