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 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.
Colombi
Marina
M
Division Biology and Genetics, University of Brescia, Italy.
Zoppi
Nicoletta
N
De Petro
Giuseppina
G
Marchina
Eleonora
E
Gardella
Rita
R
Tavian
Daniela
D
Ferraboli
Sergio
S
Barlati
Sergio
S
D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002642:Chick Embryo; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008745:Methylation; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D018076:DNA, Complementary; D005353:Fibronectins; D010455:Peptides; D011994:Recombinant Proteins; D003094:Collagen; D000409:Alanine