Myoepithelial cells are a dynamic barrier to epithelial dissemination

Orit Katarina Sirka, Eliah R. Shamir, Andrew J. Ewald

Research output: Contribution to journalArticlepeer-review

Abstract

The mammary epithelium is composed of an inner luminal and surrounding myoepithelial cell layer. The presence of cancer cells beyond the myoepithelium defines invasive breast cancer, yet the role of the myoepithelium during invasion remains unclear. We developed a 3D organotypic culture assay to model this process through lineage-specific expression of the prometastatic transcription factor Twist1. We sought to distinguish the functional role of the myoepithelium in regulating invasion and local dissemination. Myoepithelial-specific Twist1 expression induced cell-autonomous myoepithelial cell escape. Remarkably, luminal-specific Twist1 expression was rarely sufficient for escape. Time-lapse microscopy revealed that myoepithelial cells collectively restrain and reinternalize invading Twist1+ luminal cells. Barrier function correlated with myoepithelial abundance and required the expression of α-smooth muscle actin and P-cadherin. We next demonstrated that myoepithelial cells can restrain and recapture invasive cancer cells. Our data establish the concept of the myoepithelium as a dynamic barrier to luminal dissemination and implicate both smooth muscle contractility and intercellular adhesion in barrier function.

Original languageEnglish (US)
Pages (from-to)3368-3381
Number of pages14
JournalJournal of Cell Biology
Volume217
Issue number10
DOIs
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • Cell Biology

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