Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144 Journal Article


Authors: Pozios, I.; Hering, N. A.; Guenzler, E.; Arndt, M.; Elezkurtaj, S.; Knösel, T.; Bruns, C. J.; Margonis, G. A.; Beyer, K.; Seeliger, H.
Article Title: Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144
Abstract: Purpose: Interleukin 6 (IL-6), Oncostatin M (OSM), and downstream effector STAT3 are pro-tumorigenic agents in pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 signaling. SC144 is a small molecule gp130 inhibitor with anticancer activity. This study examines the gp130 expression in human PDAC specimens and the in vitro effects of SC144 in PDAC cell lines. Methods: Tissue micro-arrays were constructed from 175 resected human PDAC. The gp130 expression in tumor epithelium and stroma was determined by immunohistochemistry, and survival analysis was performed. Growth inhibition by SC144 was assessed in vitro using BrdU and MTT assays. Western blotting was performed to evaluate the SC144 effect on IL-6 and OSM signaling. Results: Gp130 was expressed in the epithelium of 78.8% and the stroma of 9.4% of the tumor samples. The median overall survival for patients with or without epithelial gp130 expression was 16.7 months and 15.9 months, respectively (p = 0.830). Patients with no stromal gp130 expression showed poorer survival than patients with stromal gp130 expression (median 16.2 and 22.9 months, respectively), but this difference did not reach significance (p = 0.144). SC144 inhibited cell proliferation and viability and suppressed IL-6- and OSM-stimulated STAT3Y705 phosphorylation in PDAC cells. Conclusion: Gp130 is expressed in the epithelium of most human PDAC, but stromal expression is rare. The small molecule gp130 inhibitor SC144 potently inhibits PDAC progression in vitro and may abrogate IL-6 or OSM/gp130/STAT3 signaling. These results suggest gp130 as a novel drug target for pancreatic cancer therapy. © 2022, The Author(s).
Keywords: immunohistochemistry; adult; cancer chemotherapy; controlled study; human tissue; protein expression; protein phosphorylation; aged; survival rate; unclassified drug; human cell; major clinical study; overall survival; clinical feature; pancreatic neoplasms; antineoplastic agent; pancreaticoduodenectomy; cell proliferation; metabolism; cell viability; stat3 protein; progression free survival; carcinoma, pancreatic ductal; in vitro study; pathology; pancreas carcinoma; minimal residual disease; pancreas tumor; western blotting; interleukin 6; interleukin-6; cytokine receptor gp130; stat3 transcription factor; pancreatic cancer; tissue microarray; epithelium; disease exacerbation; glycoproteins; glycoprotein; protein inhibitor; chemoradiotherapy; cell lysate; stat3; gp130; glycoprotein gp 130; pancreatic ductal carcinoma; humans; human; male; female; article; oncostatin m; mtt assay; sc144; sc 144
Journal Title: Journal of Cancer Research and Clinical Oncology
Volume: 149
Issue: 1
ISSN: 0171-5216
Publisher: Springer  
Date Published: 2023-01-01
Start Page: 271
End Page: 280
Language: English
DOI: 10.1007/s00432-022-04518-9
PUBMED: 36495330
PROVIDER: scopus
PMCID: PMC9889481
DOI/URL:
Notes: Article -- Export Date: 1 March 2023 -- Source: Scopus
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