HGNC Approved Gene Symbol: OSM
Cytogenetic location: 22q12.2 Genomic coordinates (GRCh38): 22:30,262,829-30,266,851 (from NCBI)
Zarling et al. (1986) isolated oncostatin M, a glycoprotein with an approximate molecular weight of 28 kD, from a conditioned medium of human leukemia cells that had been induced to differentiate into macrophage-like cells by treatment with phorbol 12-myristate 13-acetate. OSM has the ability to inhibit the growth of human A375 melanoma cells but not normal human fibroblasts. Treatment with recombinant OSM leads to the inhibition of proliferation and changes in cellular morphology of a number of tumor cell lines derived from a wide variety of tissue types (Zarling et al., 1986)..
Rose and Bruce (1991) detected significant similarities in the primary amino acid sequences and predicted secondary structures of OSM, leukemia-inhibitory factor (LIF; 159540), granulocyte colony-stimulating factor (CSF3; 138970), and interleukin-6 (IL6; 147620).
Using a panel of DNAs from interspecies somatic cell hybrids, Rose and Bruce (1991) showed that OSM, like LIF (159540), is located on human chromosome 22.
Rose et al. (1993) found that the genes for OSM and LIF were segregating when cDNA probes were hybridized to DNA from somatic cell hybrids containing defined regions of human chromosome 22. They found a contig of approximately 100 kb surrounding the 2 genes which were tandemly arranged in the same transcriptional orientation and separated by approximately 10 kb. The direction of gene transcription was telomeric to centromeric, with the OSM gene located upstream of the LIF gene. The findings constituted strong evidence that OSM and LIF resulted from duplication of a common ancestral gene.
Rose and Bruce (1991) demonstrated that OSM has the ability to inhibit the proliferation of murine M1 myeloid leukemic cells and can induce their differentiation into macrophage-like cells, a function shared by LIF, CSF3, and IL6. They proposed that these 4 molecules are structurally related members of a cytokine family that have in common the ability to modulate differentiation of a variety of cell types.
Although oncostatin M inhibits the growth of a variety of cancer and other cells, Nair et al. (1992) and Miles et al. (1992) found that it is a potent mitogen for cells derived from HIV-related Kaposi sarcoma (148000).
In exploration of the potential of oncostatin M as an inflammatory effector, Modur et al. (1997) found that oncostatin M caused an acute inflammatory reaction in vivo and that it colocalized with TNF-secreting cells in chronically inflamed human vascular tissue. It induced transmigration of human neutrophils through monolayers of endothelial cells by stimulating the expression of adhesion molecules and chemokines. The pattern of endothelial cell responses, however, significantly differed from the response to TNF (191160). Modur et al. (1997) concluded that oncostatin M, but not other IL6 family members, fulfilled Koch's postulates as an inflammatory mediator. Since its effects on endothelial cells differ significantly from established mediators like TNF-alpha, it may uniquely contribute to the inflammatory cycle.
STAT5 (see STAT5A, 601511 and STAT5B, 604260) is activated in a broad spectrum of human hematologic malignancies. Using a genetic approach, Schwaller et al. (2000) addressed whether activation of STAT5 is necessary for the myelo- and lymphoproliferative disease induced by the TEL (600618)/JAK2 (147796) fusion gene. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL/JAK2 developed a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5a/b-deficient mice expressing TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-deficient background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconstitution with bone marrow cells expressing a constitutively active mutant, Stat5a, or a single Stat5a target, murine Osm. These data defined a critical role for STAT5A/B and OSM in the pathogenesis of TEL/JAK2 disease.
Miles, S. A., Martinez-Maza, O., Rezai, A., Magpantay, L., Kishimoto, T., Nakamura, S., Radka, S. F., Linsley, P. S. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Science 255: 1432-1434, 1992. [PubMed: 1542793] [Full Text: https://doi.org/10.1126/science.1542793]
Modur, V., Feldhaus, M. J., Weyrich, A. S., Jicha, D. L., Prescott, S. M., Zimmerman, G. A., McIntyre, T. M. Oncostatin M is a proinflammatory mediator: in vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules. J. Clin. Invest. 100: 158-168, 1997. [PubMed: 9202068] [Full Text: https://doi.org/10.1172/JCI119508]
Nair, B. C., DeVico, A. L., Nakamura, S., Copeland, T. D., Chen, Y., Patel, A., O'Neil, T., Oroszlan, S., Gallo, R. C., Sarngadharan, M. G. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science 255: 1430-1432, 1992. [PubMed: 1542792] [Full Text: https://doi.org/10.1126/science.1542792]
Rose, T. M., Bruce, A. G. Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. Proc. Nat. Acad. Sci. 88: 8641-8645, 1991. [PubMed: 1717982] [Full Text: https://doi.org/10.1073/pnas.88.19.8641]
Rose, T. M., Lagrou, M. J., Fransson, I., Werelius, B., Delattre, O., Thomas, G., de Jong, P. J., Todaro, G. J., Dumanski, J. P. The genes for oncostatin M (OSM) and leukemia inhibitory factor (LIF) are tightly linked on human chromosome 22. Genomics 17: 136-140, 1993. [PubMed: 8406444] [Full Text: https://doi.org/10.1006/geno.1993.1294]
Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J. C., Williams, I. R., Lee, C.-K., Gerthner, R., Kitamura, T., Frantsve, J., Anastasiadou, E., Loh, M. L., Levy, D. E., Ihle, J. N., Gilliland, D. G. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Molec. Cell 6: 693-704, 2000. [PubMed: 11030348] [Full Text: https://doi.org/10.1016/s1097-2765(00)00067-8]
Zarling, J. M., Shoyab, M., Marquardt, H., Hanson, M. B., Lioubin, M. N., Todaro, G. J. Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc. Nat. Acad. Sci. 83: 9739-9743, 1986. [PubMed: 3540948] [Full Text: https://doi.org/10.1073/pnas.83.24.9739]