Induction of an invasive phenotype in benign tumor cells with a laminin A-chain synthetic peptide.
K-1735 clones 10 and M2 are cell lines cloned from a UV-induced murine melanoma. While both lines are highly tumorigenic, only the M2 cells are highly invasive in vitro and metastatic in vivo. Here we have exposed the clone 10 cells to the synthetic peptide PA22-2, which contains the IKVAV sequence from the A chain of laminin and which, like laminin, induces collagenase IV production and enhances metastasis formation by B16F10 cells. Zymogram analysis of conditioned media from clone 10 cells cultured on the peptide demonstrated a dose-dependent increase in collagenase IV activity. When clone 10 cells were cultured on a reconstituted basement membrane (Matrigel), this peptide caused an invasive phenotype comparable to the M2 cells. The invasive clone 10 cells were, however, unable to form lung colonies in vivo in the presence of this peptide. We conclude that this peptide represents an active site on laminin which is able to stimulate the invasiveness of this tumor cell line, but that this activity is not sufficient to confer metastatic potential.
Royce
L S
LS
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Martin
G R
GR
Kleinman
H K
HK
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D003094:Collagen; D017364:Collagenases / Q000378:metabolism; D004338:Drug Combinations; D004790:Enzyme Induction; D007797:Laminin / Q000494:pharmacology*; D046911:Macromolecular Substances; D020780:Matrix Metalloproteinase 9; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D010641:Phenotype; D011509:Proteoglycans; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D004338:Drug Combinations; D007797:Laminin; D046911:Macromolecular Substances; D010446:Peptide Fragments; D010455:Peptides; D011509:Proteoglycans; C059485:matrigel; C070425:PA22-2; D003094:Collagen; D017364:Collagenases; D020780:Matrix Metalloproteinase 9