Melanoma Histiocytic leukemia Promyelocytic leukemia T cell leukemia T cell leukemia T cell leukemia T cell leukemia T cell leukemia

Oncostatin M is a polypeptide growth regulator produced by activated T cells and phorbol ester-treated U937 cells. To identify specific cellular receptors for this factor, we have characterized the binding of lZ6Ilabeled oncostatin M to a variety of normal and malignant mammalian cells. Recombinant oncostatin M was labeled with ‘’‘1 with full retention of growth inhibitory activity on A375 melanoma cells. ‘261-Oncostatin M bound to sensitive cells in a timeand temperaturedependent fashion. Binding was specifically inhibited by unlabeled native or recombinant oncostatin M, but not by other polypeptide growth factors tested. Binding to human leukemic and normal blood cells was generally less than to nonhematopoietic cells. With four different cell lines, maximal growth inhibition by oncostatin M was achieved at less than maximal binding site occupancy. Scatchard graphs of direct binding data were curvilinear and indicated that “‘1-oncostatin M bound with higher apparent affinity at lower ‘261-oncostatin M concentrations. Using a two binding site model, affinity constants of Kdl = 11 f 11 PM and Kdz = 1000 2 380 pM were extrapolated from binding data with A375 cells, and values Of & I = 3 2 2 p M and Kd = 400 2 44 p~ from A549 cells. The major lZ6Ioncostatin M binding species in a number of mammalian cell lines was identified by chemical cross-linking as a specific protein(s) of M, = 150,000-160,000. lZ61Oncostatin M was internalized (tH = 30 min) and degraded subsequent to binding to a responsive cell line. We conclude that ”‘1-oncostatin M binding sites are receptors for oncostatin M and may be involved in growth regulation by this factor.