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.
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.
Murakami-Mori
K
K
Institute of Molecular Medicine and Technology, Huntington Memorial Hospital, Pasadena, California 91105, USA.
Taga
T
T
Kishimoto
T
T
Nakamura
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D015870:Gene Expression; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism; D008969:Molecular Sequence Data; D053683:Oncostatin M; D010452:Peptide Biosynthesis; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000032:analysis / Q000096:biosynthesis*; D018123:Receptors, Interleukin / Q000032:analysis / Q000096:biosynthesis*; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D012514:Sarcoma, Kaposi / Q000209:etiology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D053683:Oncostatin M