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Originally published In Press as doi:10.1074/jbc.M211997200 on February 11, 2003

J. Biol. Chem., Vol. 278, Issue 16, 14346-14355, April 18, 2003
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Matrix Assembly Induction and Cell Migration and Invasion Inhibition by a 13-Amino Acid Fibronectin Peptide*

Marina Colombi, Nicoletta Zoppi, Giuseppina De Petro, Eleonora Marchina, Rita Gardella, Daniela Tavian, Sergio Ferraboli, and Sergio BarlatiDagger

From the Division Biology and Genetics, University of Brescia, Brescia 25123, Italy

Fibronectin (FN) is an extracellular matrix (ECM) protein involved in tumor growth and metastasis. Five human FN cDNA segments encoding for FN fragments, all starting with the II1 repeat and ending with different C-terminal extensions, have been stably expressed in chick embryo fibroblasts (CEF). These FN cDNAs induce the formation of an organized ECM in CEF as long as they retain a sequence coding for a 13-amino acid stretch (FN13), with collagen binding activity, localized between type II2 and I7 repeats. An FN13 synthetic peptide induces in control CEF the assembly of an FN-ECM comparable with that observed in CEF-expressing FN fragments. The activity of FN13 is specific for its amino acid sequence, although the cysteine present in the 6th position can be substituted with a polar serine without affecting the induction of a fibrillar FN-ECM. A less fibrillar matrix is induced by FN13-modified peptides in which the cysteine is methylated or substituted by a non-polar alanine. FN13 induces the assembly of an FN-ECM also in Rous sarcoma virus-transformed CEF lacking the ECM and in hepatoma (SK-Hep1) and fibrosarcoma (HT-1080) human cell lines. FN13 also promotes the adhesion of CEF and Rous sarcoma virus-CEF at levels comparable with those obtained with purified intact FN. Finally, FN13 inhibits the migratory and invasive properties of tumorigenic cells, whereas intact FN favors their migration. All FN13-modified peptides show similar effects, although with reduced efficiency. None of these activities is supported by a scrambled peptide. These data suggest a possible role of FN13 in tumor growth and metastasis inhibition and its possible use as anti-tumorigenic agent.


* This work was supported by Ministero dell'Istruzione, dell'Università e della Ricerca, Centro di Eccellenza Innovazione Diagnostica e Terapeutica, and by CNR as part of the Progetto Strategico Oncologia.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Division of Biology and Genetics, Dept. of Biomedical Sciences and Biotechnology, Medical Faculty, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. Tel.: 39-030-3717240; Fax: 39-030-3701157; E-mail: barlati@med.unibs.it.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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