Chemotactic factor binding by metastatic tumour cells: evidence for a formyl-peptide receptor on a non-myelogenous cell.
Analysis of fMet-Leu-[3H]Phe binding to Walker 256 carcinosarcoma cells demonstrated both saturable and reversible binding, and indicated the presence of a single population of binding sites having an equilibrium dissociation constant: KD = 15.7 +/- 3.3 X 10(-9) M, and with 2425 +/- 204 binding sites per cell. The specificity of the binding site was investigated by competitive inhibition of fMet-Leu-[3H]Phe binding studies using 10 oligoformyl peptides. These results demonstrated an order of peptide reactivity with marked similarity in specificity to the leucocyte binding sites for the formyl-peptides. The most active peptides also had potent agonist activity as determined by their ability to increase the cells' adherence response to nylon-wool fibres. In addition, a competitive antagonist of the formyl-peptide receptor, tert-butoxy-Phe-Leu-Phe-Leu-Phe, completely abolished the adherence response induced by fMet-Leu-Phe, but had no inhibitory effect on the adherence response caused by the tumour-promoting agent, phorbol myristate acetate. These data demonstrate that formyl-peptide receptors may be more common than we have anticipated and may be found on cells not derived from the myeloid series. Furthermore, these studies advance our understanding of stimulus-coupled responses in tumour cells.
D000818:Animals; D001665:Binding Sites; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate