Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells.

Zarling, Joyce M.; Shoyab, Mohammed; Marquardt, Hans; Hanson, Marcia B.; Lioubin, Mario N.; Todaro, George J.

doi:10.1073/pnas.83.24.9739

Cited by 369 publications

(235 citation statements)

References 40 publications

(18 reference statements)

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“…In this study, we delineate the signaling mechanism of IL-6 and OSM in human A375 melanoma cells that have long been known to be growth inhibited by these cytokines (Morinaga et al, 1989;Zarling et al, 1986). We show with receptor chimeras and dominant negative forms of STATs that the gp130-mediated growth arrest of human A375 melanoma cells crucially depends on the activation of STATs.…”

Section: Introductionmentioning

confidence: 81%

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Heinrich²,

et al. 1999

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Interleukin-6 (IL-6)-type cytokines lead to growth arrest of human A375 melanoma cells. The present study demonstrates that this e ect depends on the activation of STAT transcription factors. We observed a correlation between the extent of growth inhibition exerted by IL-6, IL-6 plus soluble IL-6 receptor or oncostatin M (OSM) and the intensities of STAT3 and STAT1 signals. A truncated chimeric receptor retaining only the membrane-proximal region of gp130, the common signal transducer of IL-6-type cytokines, did neither activate STATs nor mediate growth arrest of stable transfectants. These functions were restored by the addition of short STAT recruitment modules comprising critical tyrosine residues from gp130 (Y767, Y814). A receptor carrying tyrosine module Y759 of gp130 e ectively mediated activation of the phosphatase SHP-2 but did not alter cell growth. Overexpression of dominant negative forms of STAT3 but not STAT1 abrogated the inhibitory e ect of OSM and IL-6 in A375 cells. In addition, we have identi®ed the cyclin-dependent kinase inhibitor p27/Kip1 as a novel target to be regulated by IL-6-type cytokines. Stimulation-dependent upregulation of p27 mRNA occurred STAT3-dependently. Also p27 protein accumulated which coincided with the disappearance of hyperphosphorylated retinoblastoma protein in three human melanoma cell lines sensitive to IL-6-type cytokines.

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Section: Introductionmentioning

confidence: 81%

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Heinrich²,

et al. 1999

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“…Most studies of the squamous immunophenotype of KAs demonstrate a higher degree of differentiation in KAs compared with SCCs (51)(52)(53)(54)(55)(56). Moreover, the presence of a fibrotic reaction at the interface of regressing KA and the surrounding stroma may be a reflection of the ability of OSM to affect fibroblasts (6,9,57).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Oncostatin M Expression in Keratoacanthoma and Squamous Cell Carcinoma

et al. 2000

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Oncostatin M (OSM) is a 28-kDa glycoprotein, produced by stimulated macrophages and T lymphocytes, that inhibits the proliferation and induces differentiation of a number of different cell lines derived from solid tumors. To determine whether keratoacanthoma (KA) is unique or a variant of squamous cell carcinoma (SCC), we compared the immunohistochemical expression of OSM in the tumor cells and peri-and intratumoral macrophages of 21 mature KAs, 7 regressing KAs, and 27 SCCs. An inverse correlation was identified between OSM tumor labeling and the density of OSM-labeled tumor-associated macrophages for KAs (r ‫؍‬ ؊.4; P ‫؍‬ .09). OSM tumor expression was significantly more frequent and more intense in KAs than in SCCs (95% versus 63%; P < .01). In contrast, the density of OSM-labeled macrophages was significantly higher in SCCs compared with mature KAs (7/3 high power fields versus 4/3 high power fields; P ‫؍‬ .02). These OSM-positive macrophages were predominantly located at the advancing, infiltrative margins of both neoplasms. Regressing KAs demonstrated a decreased level of OSM tumor expression compared with mature KAs (53% versus 95%; P ‫؍‬ .001), but there was no difference in density of OSMlabeled macrophages. Both the above differences and the overlapping patterns of OSM expression suggest that KAs are a variant of SCC where OSM, possibly as an autocrine factor, may mediate KA's overwhelming but not absolute tendency to involute.

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“…Oncostatin M (osm) is a multifunctional cytokine that inhibits growth of a wide range of tumor cell lines and is produced by activated monocytes and T lymphocytes (Zarling et al, 1986). cis encodes a 37 kD protein that contains a SH2 domain, which is capable to bind to phosphorylated cytokine receptors (Yoshimura et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…With this approach the genes cis (cytokine inducible SH2-containing protein; Yoshimura et al, 1995), pim-1 (Selten et al, 1986) and osm (oncostatin M; Zarling et al, 1986;Yoshimura et al, 1996) could be identi®ed as STAT5 speci®c target genes. In order to study the role of STAT5 in the signalling of the Xmrk kinase, we examined by RT ± PCR analysis if the expression of cis, pim-1 and osm is induced in BaF Hm cells upon HERmrk stimulation.…”

Section: Activation Of the Xmrk Kinase Induces Nuclear Translocation mentioning

confidence: 99%

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

et al. 1998

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Overexpression of the mutationally activated Xmrk receptor initiates the formation of hereditary malignant melanoma in the ®sh Xiphophorus. In addition to transcriptional overexpression a cell-type speci®c signal transduction is essential for Xmrk mediated tumor formation. To elucidate the consequence of Xmrk signalling and to identify target proteins that characterize the tumor phenotype, we analysed proteins that are strongly tyrosine phosphorylated in the ®sh melanoma cell line PSM. One of the most prominent phosphotyrosine proteins was found to be the signal transducer and activator of transcription STAT5. In a heterologous cell system (murine pro B-cells), activation of the Xmrk kinase in a chimeric receptor induced tyrosine phosphorylation, nuclear translocation and DNA binding of STAT5. Following receptor stimulation, expression of the STAT5 speci®c target genes cis, osm and pim-1 was induced. In Xiphophorus PSM cells STAT5 was found to be preferentially localized in the nucleus, but treatment with tyrphostin AG555, a speci®c Xmrk kinase-inhibitor, blocked nuclear localization. In these cells as well as in Xiphophorus melanoma expression of pim-1 and constitutive DNA-binding activity of STAT5 was detectable. This constitutive activity was higher in malignant than in benign melanomas, indicating that STAT5 activation is correlated with the malignancy of these tumors.

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Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells.

Cited by 369 publications

References 40 publications

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Comparison of Oncostatin M Expression in Keratoacanthoma and Squamous Cell Carcinoma

Signalling by the oncogenic receptor tyrosine kinase Xmrk leads to activation of STAT5 in Xiphophorus melanoma

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