Identification of an amino acid sequence from the laminin A chain that stimulates metastasis and collagenase IV production.
Tumor cells attach, degrade, and migrate through basement membranes as they metastasize. Laminin, a major glycoprotein of basement membranes, promotes the metastatic activity of tumor cells by stimulating the attachment and migration of the cells and their secretion of collagenase IV. We have identified a synthetic peptide of 19 amino acids (Cys-Ser-Arg-Ala-Arg-Lys-Gln-Ala-Ala-Ser-Ile-Lys-Val-Ala-Val-Ser-Ala-Asp -Arg) from the sequence of the A chain of laminin that increases experimental metastases of the lungs by murine melanoma cells. The peptide is active when injected either intravenously or intraperitoneally. The peptide increased collagenase IV activity, a key enzyme in the breakdown of basement membranes, to the same extent as laminin. This peptide represents an active site on laminin for promotion of the metastatic phenotype and generates a probe for studying the regulation of malignant activities.
Kanemoto
T
T
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Reich
R
R
Royce
L
L
Greatorex
D
D
Adler
S H
SH
Shiraishi
N
N
Martin
G R
GR
Yamada
Y
Y
Kleinman
H K
HK
D000595:Amino Acid Sequence; D000818:Animals; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D046911:Macromolecular Substances; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D003012:Microbial Collagenase / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D007797:Laminin; D046911:Macromolecular Substances; D010455:Peptides; D003012:Microbial Collagenase