Laminin-5 : function of the γ2 chain in epithelial cell adhesion and migration, and expression in epithelial cells and carcinomas
|Organizations:||University of Oulu, Faculty of Science, Department of Biology, Zoology
|Online Access:||PDF Full Text (PDF, 1.3 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:9514253426
|Publish Date:|| 1999-08-31
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic Dissertation to be presented with the assent of the Faculty of Science, University of Oulu, for public discussion in Raahensali (Auditorium L 10), Linnamaa, on Octobet 2nd, 1999, at 12 noon.
Professor Nils Brünner
Professor Jyrki Heino
Laminins are basement membrane glycoproteins consisting of three polypeptide chains α, β and γ. Until now 12 members of the protein family have been characterized and all isoforms have an αβγ chain composition, but they assemble in varying combinations of chain variants. The functional properties of laminins include cell adhesion, proliferation, differentiation, growth and migration. Laminin-5 has a chain composition of α3β3γ2 with the distribution mainly restricted to epithelial basement membranes, where its biological functions involve anchorage and locomotion of cells. The importance of this protein for the attachment of basal keratinocytes is clearly demonstrated by the fact that all genes encoding its chains have been shown to be mutated in the severe skin blistering disease Epidermolysis bullosa junctionalis.
The present study focused on investigations of the role of the laminin-5 isoform and particularly its γ2 chain in cell adhesion and migration. The role of the short arm of the laminin γ2 chain in the process of epithelial cell attachment is to serve as a kind of a bridging molecule to the extracellular environment, because it does not have any cell binding activity by itself. It was also shown that the newly synthesized γ2 chain participates in the complex process of cell migration, probably as one of the first attachment components for moving cells. Thus, as a migration and differentiation-associated molecule, laminin-5 was considered a potential marker for detection of malignant processes where cell movement plays a role. Subsequently it was shown that the γ2 chain is expressed not only in a restricted manner in human epithelial tissues, but also in a number of human epithelium-derived cancers. In some carcinomas, expression of the γ2 chain appeared to be a characteristic of cancer cells with invasive properties. Examination of over 50 dysplasias and cervical tumors revealed that γ2 chain antibodies were able to distinguish between lesions with or without invasive capacity. This is the first systematic study of epithelial cancers where γ2 chain antibodies have been shown to be a useful marker in the histopathological diagnostics. In addition, this study showed in a mouse tumor model that the γ2 chain of laminin-5 has a potential for being of use for in vivo tumor imaging.
Acta Universitatis Ouluensis. D, Medica
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