Marked stimulation of cell adhesion and motility by ladsin, a laminin-like scatter factor.
Ladsin is a large cell-adhesive protein with potent cell-scattering activity, which was recently identified in the culture of a malignant human gastric carcinoma cell line [Miyazaki, K. et al. (1993) Proc. Natl. Acad. Sci. USA 90, 11767-11771]. It is a heterotrimeric protein, containing a 140-kDa subunit similar or identical to the laminin B2t chain. Ladsin is similar to the keratinocyte-derived matrix proteins, "epiligrin" and "kalinin." In the present study, the cell-adhesion and cell-migration activities of ladsin were examined in comparison with those of three cell adhesion proteins, laminin, fibronectin, and vitronectin. Ladsin showed high cell-adhesion activity toward rat liver cell line BRL at concentrations 4-20-times lower than in the case of the other three proteins. In a monolayer culture, ladsin stimulated the migration of BRL cells about 2-times more strongly than the others, as compared at the minimal concentrations required for the maximal cell-adhesion activity. In Boyden chambers, ladsin stimulated both the chemotactic and chemokinetic migration of BRL cells. When the effect of anti-integrin antibodies on the adhesion of human fibrosarcoma cell line HT1080 was examined, the adhesion to ladsin was effectively inhibited by both the anti-integrin alpha 3 and beta 1 antibodies, but not the anti-integrin alpha 6 antibody, indicating that the primary receptor of ladsin is integrin alpha 3 beta 1. These results demonstrate that ladsin is a unique extracellular matrix component which may play a major role in cell migration.
Kikkawa
Y
Y
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University.
Umeda
M
M
Miyazaki
K
K
D000328:Adult; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D011915:Rats, Inbred BUF; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019096:Vitronectin
D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006023:Glycoproteins; D007797:Laminin; D019096:Vitronectin; D017228:Hepatocyte Growth Factor