The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis.
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, alpha 6 beta 4 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 alpha subunits of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 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.
Stahl
S
S
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL, USA.
Weitzman
S
S
Jones
J C
JC
D000906:Antibodies / Q000494:pharmacology; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D001940:Breast / Q000254:growth & development* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003896:Desmosomes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D004848:Epithelium / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D009024:Morphogenesis / Q000187:drug effects; D017474:Receptors, Laminin / Q000378:metabolism*; D015398:Signal Transduction; D000097794:Kalinin
D000906:Antibodies; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D016023:Integrins; D017474:Receptors, Laminin; D000097794:Kalinin