Keratinocyte motility induced by TGF-beta1 is accompanied by dramatic changes in cellular interactions with laminin 5.
Transforming growth factor-beta1 (TGF-beta1) has the ability to induce epithelial cell migration while stopping proliferation. In this study, we show that, concomitant to promoting migration of normal human keratinocytes in vitro, TGF-beta1 induced a marked decrease in their adhesion capacity to processed alpha3-containing laminin 5-coated surfaces. Indeed, the expression levels of alpha3 and alpha6 integrin subunit mRNA and protein, as well as the cell surface alpha3beta1 and alpha6beta4 integrins, were down-regulated. Recent studies showed that keratinocytes over express and deposit laminin 5 during migration and we have shown that laminin 5 found in the matrix of TGF-beta1 induced migrating keratinocytes is present in its unprocessed form [Décline and Rousselle, 2001: J. Cell Sci. 114:811-823]. We show here that TGF-beta1 treatment of the cells promoted a significant increase in their adhesion to the alpha3 chain carboxy-terminal LG4/5 subdomain and that this interaction is likely to be mediated by a heparan sulfate proteoglycan type of receptor. Our results indicate that alpha6beta4 and alpha3beta1 integrin interactions with laminin 5 are diminished during migration while a specific interaction occurs between an additional cellular receptor and the alpha3 LG4/5 module present on unprocessed laminin 5.
Décline
Françoise
F
Institut de Biologie et Chimie des Protéines, Lyon, France.
Okamoto
Osamu
O
Mallein-Gerin
Frédéric
F
Helbert
Bruno
B
Bernaud
Janine
J
Rigal
Dominique
D
Rousselle
Patricia
P
D002448:Cell Adhesion / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039201:Integrin alpha3beta1 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D039161:Integrin alpha6beta4 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007797:Laminin / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D017474:Receptors, Laminin / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing
D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D017474:Receptors, Laminin; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C097043:laminin alpha5