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.