Laminin receptor complementary DNA-deduced synthetic peptide inhibits cancer cell attachment to endothelium.
Stable attachment of cancer cells to the endothelium is a key step in the formation of metastasis. In this study, we have investigated the possibility that interaction between laminin and its Mr 67,000 high-affinity receptor (67 LR) could play a major role in this process. Scatchard analysis of laminin-binding studies showed that bovine aortic endothelial cells exhibit 46,000 high-affinity receptors that mediate, at least in part, the attachment of highly invasive melanoma cells. This endothelial cell-melanoma cell interaction was significantly inhibited by soluble laminin and by anti-laminin antibodies. Peptide G, an eicosapeptide derived from the complementary DNA sequence of the 67 LR precursor (IPCNNKGAHSVGLMWWMLAR) that specifically binds to laminin and presumably contains the active ligand-binding site of the receptor, specifically prevented attachment of the melanoma cells to both the bovine aortic endothelial cell monolayer and human umbilical vein endothelium. Thus, peptide G may selectively interfere with the metastatic cascade by inhibiting tumor cell attachment to endothelium via the laminin-67 LR pathway and is a potential new antimetastatic agent.
Castronovo
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Tumor Invasion and Metastasis Section, National Cancer Institute, Bethesda, Maryland 20892.
Taraboletti
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Sobel
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D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008545:Melanoma / Q000503:physiopathology*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017474:Receptors, Laminin; D014407:Tumor Cells, Cultured
D007797:Laminin; D011971:Receptors, Immunologic; D017474:Receptors, Laminin