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Updated: Apr 16, 2026
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Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix
Published on: July 10, 2016
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Mammary Branching Morphogenesis Requires Reciprocal Signaling by Heparanase and MMP-14
Angélica Maciel Gomes1,2, Ramray Bhat1, Ana Luísa Correia1
1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720.
Journal of Cellular Biochemistry
|March 5, 2015
Summary
Heparanase, an enzyme that degrades heparan sulfate, is crucial for mammary gland development. Its presence and activity promote epithelial cell invasion and branching, essential for forming the gland's structure.
Area of Science:
- Developmental Biology
- Cell Biology
- Biochemistry
Background:
- Mammary gland development involves epithelial cell invasion and extracellular matrix (ECM) remodeling.
- Heparan sulfate proteoglycans (HSPGs) are key ECM components influencing cell behavior.
- Matrix metalloproteinases (MMPs) are implicated in ECM degradation during development.
Purpose of the Study:
- To investigate the role of heparanase, a heparan sulfate-degrading enzyme, in mammary gland development.
- To understand the mechanisms by which heparanase influences epithelial cell invasion and branching.
Main Methods:
- In vivo localization studies of heparanase in mouse mammary glands.
- Three-dimensional (3D) organotypic cultures to assess heparanase function in branching.
- Analysis of mammary glands from heparanase-overexpressing and knockout mice.
- Examination of the relationship between heparanase and MMP14 levels.
Main Results:
- Heparanase is localized in growing end buds during mammary gland branching.
- Heparanase expression and activity are essential for mammary epithelial invasion and branching in 3D cultures.
- Mammary gland branching directly correlates with heparanase levels in vivo.
- A reciprocal association exists between heparanase and MMP14.
Conclusions:
- Heparanase plays a significant role in regulating mammary gland development by promoting epithelial branching.
- The findings elucidate a novel mechanism involving heparanase and MMP14 in mammary gland morphogenesis.
- This study provides insights into the enzymatic regulation of ECM remodeling during development.
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