The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis

Stephanie Stahl, Sigmund Weitzman, Jonathan C R Jones

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, α6β4 integrin and its ligand laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes when plated onto uncoated substrates. When maintained on matrigel, like their normal breast epithelial cell counterparts, MCF-10A cells undergo a branching morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction. Function blocking antibodies specific for human laminin-5 and the a subunits of its two known receptors (α3β1 and α6β4 integrin) not only inhibit hemidesmosome assembly by MCF-10A cells but also impede branching morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in particular those subunits comprising its laminin-5/integrin 'backbone', play an important role in morphogenetic events. We discuss these results in light of recent evidence that hemidesmosomes are sites involved in signal transduction.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalJournal of cell science
Volume110
Issue number1
StatePublished - Jan 1997

Keywords

  • Hemidesmosome
  • Integrin
  • Laminin

ASJC Scopus subject areas

  • Cell Biology

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