Epithelial Plasticity During Human Breast Morphogenesis and Cancer Progression

Saevar Ingthorsson, Eirikur Briem, Jon Thor Bergthorsson, Thorarinn Gudjonsson*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Understanding the complex events leading to formation of an epithelial-based organ such as the breast requires a detailed insight into the crosstalk between epithelial and stromal compartments. These interactions occur both through heterotypic cellular interactions and between cells and matrix components. While in vivo models may partially capture these complex interactions, there is a need for in- vitro models to study these events. In this review we discuss cell-cell interactions in breast development focusing on the stem cell niche and branching morphogenesis. Given the recent understanding that the basic developmental events underlying branching morphogenesis are closely related to pathways important to cancer progression, i.e. epithelial plasticity and epithelial to mesenchymal transition (EMT), we will also discuss aspects relevant to cancer progression. In cancer, the adoption of mesenchymal phenotype by the malignant cells allows stromal invasion and subsequent intravasation to blood- or lymphatic vessels, a route that is a prerequisite for metastasis. A number of publications have demonstrated that tumor initiating cells, sometimes referred to as cancer stem cells adapt an EMT phenotype that renders them more resistant to apoptosis and drug therapy. The mechanism behind this phenomenon is currently unknown but this may partially explain relapse in breast cancer patients. Increased understanding of branching morphogenesis in the breast gland and the regulation of EMT and its reverse process mesenchymal to epithelial transition (MET) may hold the keys for future development of methods/drugs that neutralize the invading properties of cancer cells.

Original languageEnglish
Pages (from-to)139-148
Number of pages10
JournalJournal of Mammary Gland Biology and Neoplasia
Issue number3-4
Publication statusPublished - 1 Dec 2016

Bibliographical note

Funding Information:
This work was supported by grants from Landspitali University Hospital Science Fund, University of Iceland Research Fund, Grant of Excellence from the Icelandic Science and Technology Policy Council-Research fund and “Göngum saman,” a supporting group for breast cancer research in Iceland ( www.gongumsaman.is ).

Publisher Copyright:
© 2016, The Author(s).

Other keywords

  • 3D cell culture
  • Breast cancer
  • EMT
  • Plasticity
  • Stem cells


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