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.
Open Access
- 1 September 1995
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 96 (3) , 1319-1327
- https://doi.org/10.1172/JCI118167
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.Keywords
This publication has 34 references indexed in Scilit:
- Interactions between oncostatin M and the IL-6 signal transducer, gp130Cytokine, 1994
- Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130.The Journal of Experimental Medicine, 1994
- Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi's cells. Evidence that this pathway is important in Kaposi cell growth.Journal of Clinical Investigation, 1993
- Inhibition of Development of Kaposi's Sarcoma-Related Lesions by a Bacterial Cell Wall ComplexScience, 1992
- Oncostatin M as a Potent Mitogen for AIDS-Kaposi's Sarcoma-Derived CellsScience, 1992
- Molecular cloning and expression of an IL-6 signal transducer, gp130Cell, 1990
- Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130Cell, 1989
- AIDS-Kaposi's Sarcoma-Derived Cells Express Cytokines with Autocrine and Paracrine Growth EffectsScience, 1989
- Receptors for T cell-replacing factor/interleukin 5. Specificity, quantitation, and its implication.The Journal of Experimental Medicine, 1988
- KAPOSIʼS SARCOMA IN ORGAN TRANSPLANT RECIPIENTS REPORT OF 20 CASESTransplantation, 1979