Oncostatin M: A Growth Regulator Produced by Differentiated Histiocytic Lymphoma Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 24; pp. 9739 - 9743
• Main Authors: Zarling, Joyce M., Shoyab, Mohammed, Marquardt, Hans, Hanson, Marcia B., Lioubin, Mario N., Todaro, George J.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1986; National Acad Sciences
• Subjects: Amino Acid Sequence; Amino acids; Biological and medical sciences; Biological Products - isolation & purification; Biological Products - pharmacology; Cell Differentiation; Cell Division - drug effects; Cell growth; Cell Line; Cell lines; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cytokines; Elution; Fibroblasts - cytology; Fundamental and applied biological sciences. Psychology; Growth inhibitors; Growth Inhibitors - isolation & purification; Humans; Lymphoma, Large B-Cell, Diffuse - analysis; Lymphoma, Large B-Cell, Diffuse - physiopathology; Macrophages - physiology; Melanoma; Melanoma, Experimental - pathology; Molecular and cellular biology; Molecular Weight; Natural killer cells; Neurons; Oncostatin M; Peptides - isolation & purification; Tetradecanoylphorbol Acetate - pharmacology; Tumor cell line; Tumors; Proteins; Cell culture; Purification; Histiocyte; Growth; Production; HPLC chromatography; Inhibition; Cell differentiation; Lymphoma; Tumor cell; Gel permeation chromatography
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.24.9739

A polypeptide termed oncostatin M, which inhibits the replication of A375 melanoma and other human tumor cells, but not normal human fibroblasts, has been isolated from serum-free supernatants of U-937 histiocytic lymphoma cells that have been induced to differentiate into macrophage-like cells following treatment with the phorbol ester phorbol 12-myristate 13-acetate. No such growth inhibitory activity is detected in the supernatant of untreated U-937 cells, indicating that the protein is induced or increased in expression in the phorbol ester-induced differentiated cells. Oncostatin M is stable between pH 2 and 11 and after heating for 1 hr at 56 degrees C but is not stable at 90 degrees C. Purification of oncostatin M has been achieved by gel chromatography and reversed-phase HPLC, using sequentially acetonitrile and n-propanol in the presence of aqueous trifluoroacetic acid. The apparent molecular weight of oncostatin M is ≈ 18,000, as determined by gel chromatography, and 28,000, as determined by polyacrylamide gel electrophoresis. The amino-terminal amino acid sequence of the purified polypeptide has been determined. No substantial sequence homology between oncostatin M and other proteins was found, including other tumor cell inhibitory proteins produced by mononuclear cells. Oncostatin M, therefore, appears to represent a distinct cell growth regulator.