Laminin 10/11: an alternative adhesive ligand for epidermal keratinocytes with a functional role in promoting proliferation and migration

N Pouliot, NA Saunders, P Kaur - Experimental dermatology, 2002 - Wiley Online Library
N Pouliot, NA Saunders, P Kaur
Experimental dermatology, 2002Wiley Online Library
We have investigated the expression and function of the isoforms of laminin bearing the α5
chain, ie 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‐α5 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 (α5 chain) appeared …
Abstract: We have investigated the expression and function of the isoforms of laminin bearing the α5 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‐α5 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 (α5 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 α3β1 and α6β4 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.
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