Enhancement of interleukin 6 cytostatic effect on human breast carcinoma cells by soluble IL-6 receptor from urine and reversion by monoclonal antibody.
Interleukin 6 receptor soluble urinary protein (IL-6-R-SUP), a purified urinary protein binding IL-6 and identified as a truncated 50 kDa soluble form of the 80 kDa IL-6 cellular receptor, was tested for its biological activity. Addition of IL-6-R-SUP enhances the growth stimulation of mouse plasmacytoma T1165 by subliminal concentrations of human recombinant IL-6. Since this effect could be due to a lower affinity of human IL-6 for the mouse cell receptor, we tested the effect of IL-6-R-SUP on human cells. We show that the growth-inhibitory effect of IL-6 on breast carcinoma cells is enhanced by addition of IL-6-R-SUP to these human cells although they possess abundant IL-6 receptors. With IL-6-R-SUP, complete growth inhibition by IL-6 could be achieved and the cells became more sensitive to low levels of IL-6. These effects were prevented by a monoclonal antibody against IL-6-R-SUP which blocks IL-6 binding to cells. The naturally occurring IL-6-R-SUP may help to increase the growth-regulatory action of IL-6.
Novick
D
D
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Shulman
L M
LM
Chen
L
L
Revel
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology* / Q000652:urine; D010954:Plasmacytoma / Q000473:pathology*; D011971:Receptors, Immunologic / Q000276:immunology / Q000302:isolation & purification*; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors