Universität zu Köln

Pozios, Ioannis ORCID: 0000-0002-3462-9822, Hering, Nina A., Guenzler, Emily, Arndt, Marco, Elezkurtaj, Sefer, Knosel, Thomas, Bruns, Christiane J., Margonis, Georgios A., Beyer, Katharina and Seeliger, Hendrik ORCID: 0000-0002-5937-052X (2023). Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144. J. Cancer Res. Clin. Oncol., 149 (1). S. 271 - 281. NEW YORK: SPRINGER. ISSN 1432-1335

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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 STAT3(Y705) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pozios, Ioannis UNSPECIFIED orcid.org/0000-0002-3462-9822 UNSPECIFIED Hering, Nina A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenzler, Emily UNSPECIFIED UNSPECIFIED UNSPECIFIED Arndt, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Elezkurtaj, Sefer UNSPECIFIED UNSPECIFIED UNSPECIFIED Knosel, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Margonis, Georgios A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beyer, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeliger, Hendrik UNSPECIFIED orcid.org/0000-0002-5937-052X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-686435
DOI:	10.1007/s00432-022-04518-9
Journal or Publication Title:	J. Cancer Res. Clin. Oncol.
Volume:	149
Number:	1
Page Range:	S. 271 - 281
Date:	2023
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1335
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERLEUKIN-6; INFLAMMATION; STATISTICS; ACTIVATION; DISCOVERY; CYTOKINES; DISEASES; PROFILE Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68643