A cell binding domain from the alpha3 chain of type IV collagen inhibits proliferation of melanoma cells.
Our previous studies have shown that a peptide corresponding to the residue sequence 185-203 of the NC1 domain of the alpha3 chain of basement membrane collagen (type IV) inhibits the activation of polymorphonuclear leukocytes. Peptides from the same region of the alpha1, alpha2, alpha4, and alpha5(IV) chains did not exhibit this property. Because of the intimate relationship between metastasizing neoplastic cells and vascular as well as epithelial basement membranes, we measured the cell adhesion-promoting activity of peptides from the NC1 domain of type IV collagen and their effect on proliferation of human melanoma cells. We found that peptide alpha3(IV)185-203 (CNYYSNSYSFWLASLNPER) not only promotes adhesion of human melanoma cells but also inhibits their proliferation. Adhesion increased by 50-60% over control. Melanoma cell proliferation was inhibited by 40% when cells were grown in a medium containing 5 microg/ml peptide for 5 days. Studies showed that replacement of serine in position 189 or 191 by alanine resulted in significantly reduced adhesion. Similarly, serine replacement resulted in reduced ability to inhibit proliferation. Our data suggest that a region of the NC1 domain of the alpha3(IV) chain, contained within the sequence 185-203, not only specifically promotes adhesion but also inhibits proliferation of melanoma cells. These properties appear to be dependent on the presence of the triplet sequence -SNS- (residues 189-191), which is unique to the alpha3 chain and may represent an important functional epitope.
Han
J
J
Connective Tissue Research Institute, Department of Medicine, University of Pennsylvania, and the University City Science Center, Philadelphia, Pennsylvania 19104, USA.
Ohno
N
N
Pasco
S
S
Monboisse
J C
JC
Borel
J P
JP
Kefalides
N A
NA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D003094:Collagen