Laminin 10/11: an alternative adhesive ligand for epidermal keratinocytes with a functional role in promoting proliferation and migration.
We have investigated the expression and function of the isoforms of laminin bearing the alpha5 chain, i.e. laminin-10/11 in neonatal and adult human skin. By immunostaining human skin derived from a variety of anatomic sites, we found that the laminin-alpha5 chain is expressed abundantly in the basement membrane underlying the interfollicular epidermis and the blood vessels in the dermis. Interestingly, while the expression level of the well-studied laminin-5 isoform did not change significantly with age, laminin-10/11 (alpha5 chain) appeared to decrease in the basement membrane underlying the epidermis, in adult skin. In contrast, the levels of laminin-10/11 in the basement membrane underlying blood vessels remained unchanged in neonatal vs. adult skin. Importantly, in vitro cell adhesion assays demonstrated that laminin-10/11 is a potent adhesive substrate for both neonatal and adult keratinocytes and that this adhesion is mediated by the alpha3beta1 and alpha6beta4 integrins. Adhesion assays performed with fractionated basal keratinocytes showed that stem cells, transit amplifying cells and early differentiating cells all adhere to purified laminin-10/11 via these receptors. Further, laminin-10/11 provided a proliferative signal for neonatal foreskin keratinocytes, adult breast skin keratinocytes, and even a human papillomavirus type-18 transformed tumorigenic keratinocyte cell line in vitro. Finally, laminin-10/11 was shown to stimulate keratinocyte migration in an in vitro wound healing assay. These results provide strong evidence for a functional role for laminin-10/11 in epidermal proliferation during homeostasis, wound healing and neoplasia.
D000328:Adult; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007231:Infant, Newborn; D039201:Integrin alpha3beta1 / Q000378:metabolism; D039161:Integrin alpha6beta4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008024:Ligands; D020033:Protein Isoforms / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D008024:Ligands; D020033:Protein Isoforms; D000097794:Kalinin; C119013:laminin 10; C097043:laminin alpha5