AIDS-associated Kaposi's sarcoma (KS) cells express oncostatin M (OM)-specific receptor but not leukemia inhibitory factor/OM receptor or interleukin-6 receptor. Complete block of OM-induced KS cell growth and OM binding by anti-gp130 antibodies.

Abstract

Oncostatin M (OM), which shares functional similarity and structural homology to leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), functions as a potent growth factor for AIDS-associated Kaposi's sarcoma-derived cells (AIDS-KS cells). OM was also suggested to bind to the LIF receptor (LIF/OM receptor), which consists of a signal transducing subunit for LIF and IL-6 (gp130) and a LIF receptor alpha-subunit. Recent studies indicate that IL-6 has growth-stimulating activity for AIDS-KS cells. However, we find that AIDS-KS cell growth is exclusively induced by OM and not by LIF or IL-6. We also observed the lack of binding properties of AIDS-KS cells for LIF and IL-6. Scatchard plots revealed the existence of two affinity classes of OM receptor sites on AIDS-KS cells, with Kd values of 6-12 pM (high affinity) and 521-815 pM (low affinity). In competition binding studies, we find that the OM-specific receptor, but not the LIF/OM receptor, contributes to the OM-specific growth stimulation of AIDS-KS cells. We also noted that anti-gp130 antibodies can completely abolish OM-induced growth stimulation of AIDS-KS cells as well as OM binding to AIDS-KS cells. PCR amplification clearly revealed high levels of gp130 expression in AIDS-KS cells, while the transcript of LIF receptor alpha-subunit or IL-6 receptor alpha-subunit was not observed. Therefore, we conclude that (a) AIDS-KS cells express the OM-specific receptor with high and low affinity, but not the LIF/OM receptor; (b) gp130 on AIDS-KS cells plays a key role in OM binding and signaling on the OM-specific receptor; and (c) the lack of biological response of AIDS-KS cells to IL-6 and LIF can be explained by the absence of the IL-6 and LIF/OM receptors. All this evidence shows the correlation of OM-specific biological activity with expression of the OM-specific receptor and the involvement of gp130 on this receptor, as based on findings in in vitro growth assays and binding experiments for AIDS-KS cells.

• Authors: K Murakami-Mori, T Taga, T Kishimoto, S Nakamura
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 96 Issue 3 Pg. 1319-27 (Sep 1995) ISSN: 0021-9738 [Print] United States
• PMID: 7657807 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• DNA Primers
• Growth Inhibitors
• Interleukin-6
• LIF protein, human
• LIFR protein, human
• Leukemia Inhibitory Factor
• Leukemia Inhibitory Factor Receptor alpha Subunit
• Lymphokines
• OSM protein, human
• Peptides
• Receptors, Cytokine
• Receptors, Interleukin
• Receptors, Interleukin-6
• Receptors, OSM-LIF
• Receptors, Oncostatin M
• Oncostatin M

Topics

• Acquired Immunodeficiency Syndrome (complications)
• Antibodies, Monoclonal (pharmacology)
• Base Sequence
• Cell Division (drug effects)
• Cell Line
• DNA Primers
• Gene Expression
• Growth Inhibitors (biosynthesis, metabolism, pharmacology)
• Humans
• Interleukin-6
• Kinetics
• Leukemia Inhibitory Factor
• Leukemia Inhibitory Factor Receptor alpha Subunit
• Lymphokines (metabolism)
• Molecular Sequence Data
• Oncostatin M
• Peptide Biosynthesis
• Peptides (metabolism, pharmacology)
• Polymerase Chain Reaction
• Receptors, Cytokine (analysis, biosynthesis)
• Receptors, Interleukin (analysis, biosynthesis)
• Receptors, Interleukin-6
• Receptors, OSM-LIF
• Receptors, Oncostatin M
• Sarcoma, Kaposi (etiology, metabolism)