AIDS-ASSOCIATED KAPOSIS-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

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 K-d 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.