Cited by 178Cytokine Signaling Pathways and InteractionsProstate Cancer Treatment and ResearchCancer Cells and Metastasis

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JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-like Cells

Kroon, Paula, Berry, Paul A., Stower, Michael J., Rodrigues, Greta, Mann, Vincent M., Simms, Matthew, Bhasin, Deepak, Chettiar, Somsundaram, Li, Chenglong, Li, Pui-Kai, Maitland, Norman J., Collins, Anne T.·2013·Cancer Research

DOI 10.1158/0008-5472.can-13-0874

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Abstract

Interleukin (IL)-6 overexpression and constitutive STAT3 activation occur in many cancers, including prostate cancer. However, their contribution to prostate stem and progenitor cells has not been explored. In this study, we show that stem-like cells from patients with prostate cancer secrete higher levels of IL-6 than their counterparts in non-neoplastic prostate. Tumor grade did not influence the levels of expression or secretion. Stem-like and progenitor cells expressed the IL-6 receptor gp80 with concomitant expression of pSTAT3. Blockade of activated STAT3, by either anti-IL-6 antibody siltuximab (CNTO 328) or LLL12, a specific pSTAT3 inhibitor, suppressed the clonogenicity of the stem-like cells in patients with high-grade disease. In a murine xenograft model used to determine the in vivo effects of pSTAT3 suppression, LLL12 treatment effectively abolished outgrowth of a patient-derived castrate-resistant tumor. Our results indicate that the most primitive cells in prostate cancer require pSTAT3 for survival, rationalizing STAT3 as a therapeutic target to treat advanced prostate cancer. Cancer Res; 73(16); 5288–98. ©2013 AACR.

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Authors: Kroon, P., Berry, P. A., Stower, M. J., Rodrigues, G., Mann, V. M., Simms, M., Bhasin, D., Chettiar, S., Li, C., Li, P.-K., Maitland, N. J., & Collins, A. T.
Affiliations: York Hospital (GB)
ORCID: Li, Chenglong
Li, Pui-Kai
Maitland, Norman J.
Collins, Anne T.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2013-08-13
Volume: 73
Issue: 16
Pages: 5288-5298
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-13-0874
OpenAlex: W2069303628
Cited by: 175
References: 49
Citations by year: 2026: 8 · 2025: 4 · 2024: 10 · 2023: 13 · 2022: 13 · 2021: 12 · 2020: 10 · 2019: 13 · 2018: 13 · 2017: 15 · 2016: 19 · 2015: 26 · 2014: 18 · 2013: 1
FWCI: 11.41
Type: journal article
Language: en
Open access: closed
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: Prostate Cancer UK (PG12-01)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: prostate cancer, cancer stem-like cells, STAT3 activation, interleukin-6, siltuximab, tumor initiation, castration-resistant prostate cancer, therapeutic target
MeSH terms: Aged, Aged, 80 and over, Animals, Anthraquinones, Antibodies, Monoclonal, Humans, Male, Middle Aged, Sulfonamides, Neoplastic Stem Cells, Interleukin-6, Receptors, Interleukin-6, Cell Line, Tumor, STAT3 Transcription Factor, Mice, Janus Kinases, Prostatic Neoplasms, Castration-Resistant

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JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-like Cells

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