Oncostatin M promotes proliferation of ovarian cancer cells through signal transducer and activator of transcription 3

Abstract

Oncostatin M (OSM), a pleiotropic cytokine, has been shown to have distinctive effects in different tissues. In ovarian carcinoma, it is commonly co-expressed together with its receptors but its precise role and the underlying molecular mechanism governing its activity remains unclear. The aim of the present study was to investigate the function of the recombinant human OSM (rH-OSM) in human ovarian cancer. The study demonstrated that rH-OSM promotes the proliferation of SKOV3 ovarian cancer cells. Western blot analysis showed that phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), phosphorylated-extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) and p-p38 protein levels increased in the cell lines treated with rH-OSM. Proliferation in SKOV3 cells induced by rH-OSM was suppressed by inhibitors of p-p38 or p-ERK1/2. Western blot analysis showed that p-STAT3 protein levels decreased in SKOV3 cells treated with inhibitors of p-p38 prior to treatment with rH-OSM. Also, p-STAT3 levels did not increase in cells treated with inhibitors of ERK1/2 prior to treatment with rH-OSM. Cell proliferation was moderately increased, and p-ERK1/2 and p-p38 protein expression were similarly affected in STAT3-RNAi knocked-down SKOV3 cells treated with rH-OSM compared to the control group. The data demonstrate that the growth-promoting activity of rH-OSM may be mediated through different signaling pathways. ERK1/2 and p38 proteins regulate STAT3 expression in SKOV3 cells, while STAT3 may be pivotal to the proliferation of SKOV3 cells in vitro.

Cancer Stem Cell Plasticity Drives Therapeutic Resistance

“…For example, our laboratory has studied how Oncostatin M (OSM) induces aggressive cancer cell properties implicated in poor patient outcomes. Elevated levels of OSM in the TME are associated with highly aggressive metastatic cancers and an increased risk of tumor recurrence (chemotherapy resistance) in a variety of tumor types [ 61 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. OSM in the TME may originate from immune cells, adipose tissue, as well as cancer cells [ 84 , 85 , 86 , 87 , 88 , 89 ].…”

Effects of arecoline on proliferation of oral squamous cell carcinoma cells by dysregulating c-Myc and miR-22, directly targeting oncostatin M

“…Some reports indicated that OSM inhibits tumor growth and metastasis in melanoma [ 12 ], lung cancer [ 13 ], etc. Inversely, OSM has been reported to induce tumor growth and metastasis in ovarian cancer [ 14 ], breast cancer [ 15 ] and osteosarcoma [ 16 ]. The function of dysregulated endogenous OSM in cancer cell lines, including in OSCC cell lines, is still unknown.…”

CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate

“…Besides CD83 , a large number of the CD83 highly-associated genes (Person correlation >0.5, p < 0.01) within ovarian cancer transcriptome showed higher expression in ovarian cancer cells, especially in the EpCAM + /CD45 + subtypes ( Figure S1 ). CD83 highly-associated genes, such as ITGAM , IL1B , CYBB , PIK3R5 , BTK, and OSM , ectopically express in ovarian cancer cells or tissues, involving in ovarian cancer progression, hypoxia networks, and the development of chemoresistance [ 44 , 45 , 46 , 47 , 48 , 49 ]. Finally, we found that ovarian cancer patients’ survival inversely correlated with the level of CD83 expression in 907 ovarian cancer patients (low CD83 expression: 652, the high expression: 255), as patients with high CD83 expression lived significantly shorter compared with their counterparts with low CD83 expression ( Figure 1 d).…”