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Published 22 December 2003. doi:10.1083/jcb.200309105
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© The Rockefeller University Press, 0021-9525/2003/12/1363 $8.00
The Journal of Cell Biology, Volume 163, Number 6, 1363-1374


Article

Latent TGF-ß binding protein LTBP-2 decreases fibroblast adhesion to fibronectin

Marko Hyytiäinen and Jorma Keski-Oja

Departments of Virology and Pathology, The Haartman Institute and Helsinki University Hospital, University of Helsinki, Helsinki FIN-00014, Finland

Address correspondence to Jorma Keski-Oja, Department of Pathology, P.O. Box 63, Biomedicum Helsinki, University of Helsinki, Helsinki FIN-00014, Finland. Tel.: 358-9-191-25566. Fax: 358-9-191-25573. email: jorma.keski-oja{at}helsinki.fi

We have analyzed the effects of latent TGF-ß binding protein 2 (LTBP-2) and its fragments on lung fibroblast adhesion. Quantitative cell adhesion assays indicated that fibroblasts do not adhere to full-length LTBP-2. Interestingly, LTBP-2 had dominant disrupting effects on the morphology of fibroblasts adhering to fibronectin (FN). Fibroblasts plated on LTBP-2 and FN substratum exhibited less adherent morphology and displayed clearly decreased actin stress fibers than cells plated on FN. These cells formed, instead, extensive membrane ruffles. LTBP-2 had no effects on cells adhering to collagen type I. Fibroblasts adhered weakly to the NH2-terminal fragment of LTBP-2. Unlike FN, this fragment did not augment actin stress fiber formation. Interestingly, the adhesion-mediating and cytoskeleton-disrupting effects were localized to the same NH2-terminal proline-rich region of LTBP-2. LTBP-2 and its antiadhesive fragment bound to FN in vitro, and the antiadhesive fragment associated with the extracellular matrix FN fibrils. These observations reveal a potentially important role for LTBP-2 as an antiadhesive matrix component.

Key Words: extracellular matrix; LTBP; cell adhesion; antiadhesion; fibronectin


Abbreviations used in this paper: FN, fibronectin; LTBP-2, latent TGF-ß binding protein 2; MAGP, microfibril-associated glycoprotein; SL, small latent.


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