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.