Increased Expression of the Interleukin-11 Receptor and Evidence of STAT3 Activation in Prostate Carcinoma

Campbell, Cara L.; Jiang, Zhong; Savarese, Diane M.F.; Savarese, Todd M.

doi:10.1016/s0002-9440(10)63940-5

Cited by 151Cytokine Signaling Pathways and InteractionsProstate Cancer Treatment and ResearchTGF-β signaling in diseases

Increased Expression of the Interleukin-11 Receptor and Evidence of STAT3 Activation in Prostate Carcinoma

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Campbell, Cara L., Jiang, Zhong, Savarese, Diane M.F., Savarese, Todd M.·2001·The American Journal of Pathology

DOI 10.1016/s0002-9440(10)63940-5PMC PMC1850253

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Abstract

Previous investigations have shown that interleukin-6, a member of the JAK-STAT activating family of cytokines, plays an important role in prostate carcinoma. Here we demonstrate the co-expression of another member of this cytokine family, interleukin-11 (IL-11), and components of its receptor (interleukin-11 receptor; IL-11R), ie, IL-11Ralpha (involved in ligand recognition), and gp130 (involved in signal transduction) in cultured normal and malignant prostate-derived epithelial cell lines. In the DU-145 prostate carcinoma cell line, rhIL-11 stimulates a transient and dose-dependent increase in the tyrosine 705-phosphorylated, active form of STAT3 (STAT3 P-Tyr705), involved in the downstream signaling of IL-11R and other members of the gp130-dependent receptors. The ability of IL-11 to activate STAT3 in prostate-derived cells may be mechanistically important, given recent data suggesting that constitutively activated STAT3 may be associated with the malignant phenotype. In 51 human primary tissues derived from normal prostate, benign prostatic hyperplasia, and prostate carcinomas, IL-11Ralpha and gp130 were commonly expressed, with a statistically significant elevation in the expression of IL-11Ralpha in prostate carcinoma. Also, the tyrosine-phosphorylated, activated form of STAT3 was observed more prominently in the nuclei of cells residing in malignant glands compared to those in nonmalignant samples. Thus, the IL-11 receptor system is up-regulated in prostate carcinoma, and may be one part of a cytokine network that maintains STAT3 in its activated form in these tissues.

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IL-11 specifically binds IL-11Rα and activates signaling pathways involved in adipogenesis, osteoclastogenesis, neurogenesis, and megakaryocyte maturation and platelet production.
“Interleukin-11 (IL-11), a member of a family of pleiotropic cytokines [120], specifically binds to IL-11 receptor α-chain (IL-11Rα) and active the signaling pathways involved in adipogenesis, osteoclastogenesis, neurogenesis, and megakaryocyte maturation and platelet production [121].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [120]
Third-generation B7-H3 CAR-T cells killed tumor cells in vitro and in vivo in a patient-derived xenograft model of osteosarcoma.
“Zhang et al. conducted the third-generation CAR-T cells targeting B7-H3 and proved the killing effects for tumor cells in vitro and in vivo using the patientderived xenografts (PDXs) model of osteosarcoma [116–125].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [120]

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Abstract 751: Characterization of STAT3 activation in human prostate cancer
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The Activation status of STAT3/IL-6/AKT signaling pathways in Human Prostate Cells
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Authors: Campbell, C. L., Jiang, Z., Savarese, D. M. F., & Savarese, T. M.
Affiliations: University of Massachusetts Chan Medical School (US)
Corresponding author: Savarese, Todd M.
Venue: The American Journal of Pathology
Publisher: Elsevier BV
Published: 2001-01
Volume: 158
Issue: 1
Pages: 25-32
ISSN: 0002-9440 (ISSN-L)
DOI: 10.1016/s0002-9440(10)63940-5
PMC: PMC1850253
OpenAlex: W2009228236
Cited by: 151
References: 48
Citations by year: 2026: 2 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 8
FWCI: 5.61
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: American Journal Of Pathology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: interleukin-11, gp130, STAT3 activation, prostate cancer, JAK/STAT signaling, cytokine receptor expression, benign prostatic hyperplasia, DU145 cells, tyrosine phosphorylation
MeSH terms: Adenocarcinoma, Cell Line, DNA-Binding Proteins, Humans, Hyperplasia, Immunohistochemistry, Male, Phosphorylation, Prostate, Prostatic Neoplasms, RNA, Messenger, Tumor Cells, Cultured, Tyrosine, Blotting, Western, Trans-Activators, Gene Expression Regulation, Neoplastic, Interleukin-11, Receptors, Interleukin, STAT3 Transcription Factor, Receptors, Interleukin-11, Interleukin-11 Receptor alpha Subunit

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Increased Expression of the Interleukin-11 Receptor and Evidence of STAT3 Activation in Prostate Carcinoma

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