Journal ArticleDOI
Oncostatin M Receptor-Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth.
Anjali Geethadevi,Ajay Nair,Deepak Parashar,Zhiqiang Ku,Wei Xiong,Hui Deng,Yongsheng Li,Jasmine George,Donna McAllister,Yunguang Sun,Ishaque P. Kadamberi,Prachi Gupta,Michael B. Dwinell,William H. Bradley,Janet S. Rader,Hallgeir Rui,Robert F. Schwabe,Ningyan Zhang,Sunila Pradeep,Zhiqiang An,Pradeep Chaluvally-Raghavan +20 more
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TLDR
In this article, the role of the oncostatin M receptor (OSMR) in promoting ovarian cancer cell proliferation and metastasis by activating STAT3 signaling and demonstrates the preclinical efficacy of antibody-based OSMR targeting for ovarian cancer treatment.Abstract:
Although patients with advanced ovarian cancer may respond initially to treatment, disease relapse is common, and nearly 50% of patients do not survive beyond five years, indicating an urgent need for improved therapies. To identify new therapeutic targets, we performed single-cell and nuclear RNA-seq data set analyses on 17 human ovarian cancer specimens, revealing the oncostatin M receptor (OSMR) as highly expressed in ovarian cancer cells. Conversely, oncostatin M (OSM), the ligand of OSMR, was highly expressed by tumor-associated macrophages and promoted proliferation and metastasis in cancer cells. Ovarian cancer cell lines and additional patient samples also exhibited elevated levels of OSMR when compared with other cell types in the tumor microenvironment or to normal ovarian tissue samples. OSMR was found to be important for ovarian cancer cell proliferation and migration. Binding of OSM to OSMR caused OSMR-IL6ST dimerization, which is required to produce oncogenic signaling cues for prolonged STAT3 activation. Human monoclonal antibody clones B14 and B21 directed to the extracellular domain of OSMR abrogated OSM-induced OSMR-IL6ST heterodimerization, promoted the internalization and degradation of OSMR, and effectively blocked OSMR-mediated signaling in vitro. Importantly, these antibody clones inhibited the growth of ovarian cancer cells in vitro and in vivo by suppressing oncogenic signaling through OSMR and STAT3 activation. Collectively, this study provides a proof of principle that anti-OSMR antibody can mediate disruption of OSM-induced OSMR-IL6ST dimerization and oncogenic signaling, thus documenting the preclinical therapeutic efficacy of human OSMR antagonist antibodies for immunotherapy in ovarian cancer. SIGNIFICANCE: This study uncovers a role for OSMR in promoting ovarian cancer cell proliferation and metastasis by activating STAT3 signaling and demonstrates the preclinical efficacy of antibody-based OSMR targeting for ovarian cancer treatment.read more
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The role of IL-6/JAK2/STAT3 signaling pathway in cancers
TL;DR: In this article , the relationship between IL-6/JAK2/STAT3 signaling pathway and liver cancer, breast cancer, colorectal cancer, gastric cancer, lung cancer, pancreatic cancer and ovarian cancer was investigated.
Journal ArticleDOI
Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance
Deepak Parashar,Anjali Geethadevi,Sonam Mittal Sonam Mittal,Lindsey McAlarnen,Jasmine George,Ishaque P. Kadamberi,Prachi Gupta,Denise Uyar,Elizabeth Hopp,Holli M. Drendel,E. Bishop,William H. Bradley,Janet S. Rader,Sunila Pradeep,Pradeep Chaluvally-Raghavan +14 more
TL;DR: The endometrioid subtype ovarian cancer cell line named ‘MCW-OV-SL-3’, developed from the ovary of a 70-year-old patient with stage 1A endometRIoid adenocarcinoma of the Ovary, is an excellent model to study the mechanism of cancer stemness and chemoresistance in endometioid ovarian cancer.
Journal ArticleDOI
Gp130-Mediated STAT3 Activation Contributes to the Aggressiveness of Pancreatic Cancer through H19 Long Non-Coding RNA Expression
Norihiko Sasaki,Kazumi Hirano,Yuuki Shichi,Fujiya Gomi,Hisashi Yoshimura,Akira Matsushita,Masashi Toyoda,Toshiyuki Ishiwata +7 more
TL;DR: It is proposed that inhibition of the gp130/STAT3 pathway provides a promising strategy for targeting CSCs for the treatment of PDAC and may eventually facilitate invasion and metastasis, two hallmarks of malignancy.
Journal ArticleDOI
SRRM1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the JAK/STAT signaling pathway.
Xiao-qing Song,Jianhua Ma +1 more
TL;DR: In this article , the regulatory effect of serine/arginine repetitive matrix 1 (SRRM1) on hepatocellular carcinoma (HCC) and its potential pathway was explored through GSEA enrichment analysis and GeneMANIA protein-protein interaction network.
Journal ArticleDOI
Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
Sarah McCollum,Austen Kalivas,Matthew Kirkham,Kaden Kunz,J. Okojie,Adriene Pavek,Jared J. Barrott +6 more
TL;DR: It was found that OSMR is upregulated in SS by RNAseq analysis and quantitative PCR, highlighting its potential in the treatment of SS, and radioimmune therapy was synthesized for use in OSMR expressing SS and it was demonstrated that this drug is stable, while capable of efficient OSMR binding and isotope capture.
References
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Journal ArticleDOI
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