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