Matrix assembly induction and cell migration and invasion inhibition by a 13-amino acid fibronectin peptide

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 FNECM
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.