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JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-like Cells
Published version of a preprint
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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“The IL-6/JAK/STAT3 signalling pathway plays an important role in human malignancies such as CRC.12,15,46,48,49”
From PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells (2022) · cites this paper as [49]
Citations
Cites
Prospective identification of tumorigenic breast cancer cells
Al‐Hajj, M., Wicha, M. S., Benito‐Hernández, A., Morrison, S. J., & Clarke, M. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0530291100 · Cited by 10,579
Identification of human brain tumour initiating cells
Singh, S. K., Hawkins, C. E., Clarke, I. D., Squire, J. A., Bayani, J., Hide, T., Henkelman, R. M., Cusimano, M. D., & Dirks, P. B. (2004) · Nature · doi:10.1038/nature03128 · Cited by 7,564
Bonnet, D. A., & Dick, J. E. (1997) · Nature Medicine · doi:10.1038/nm0797-730 · Cited by 7,197
Jemal, A., Murray, T., Ward, E., Samuels, A., Tiwari, R. C., Ghafoor, A., Feuer, E. J., & Thun, M. J. (2005) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.55.1.10 · Cited by 4,186
A human colon cancer cell capable of initiating tumour growth in immunodeficient mice
O'Brien, C. A., Pollett, A. F., Gallinger, S., & Dick, J. E. (2006) · Nature · doi:10.1038/nature05372 · Cited by 4,174
Identification of Pancreatic Cancer Stem Cells
Li, C., Heidt, D. G., Dalerba, P. D., Burant, C., Zhang, L., Adsay, V. N., Wicha, M. S., Clarke, M. F., & Simeone, D. M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2030 · Cited by 3,419
Self-citationProspective Identification of Tumorigenic Prostate Cancer Stem Cells
Collins, A. T., Berry, P. A., Hyde, C. F., Stower, M. J., & Maitland, N. J. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2018 · Cited by 2,821
Self-citationBromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
HEINRICH, P. C., BEHRMANN, I., MÜLLER-NEWEN, G., SCHAPER, F., & GRAEVE, L. (1998) · Biochemical Journal · doi:10.1042/bj3340297 · Cited by 2,130
Hu, Y., & Smyth, G. K. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.06.008 · Cited by 2,084
TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway
Schindler, C., & Darnell, J. E. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003201 · Cited by 1,808
Identification and expansion of the tumorigenic lung cancer stem cell population
Eramo, A., Lotti, F., Sette, G., Pilozzi, E., Biffoni, M., Virgilio, A. D., Conticello, C., Ruco, L., Peschle, C., & Maria, R. D. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402283 · Cited by 1,707
Histologic grading of prostate cancer: A perspective
Gleason, D. F. (1992) · Human Pathology · doi:10.1016/0046-8177(92)90108-f · Cited by 1,050
CD133, a novel marker for human prostatic epithelial stem cells
Richardson, G. D., Robson, C. N., Lang, S., Neal, D. E., Maitland, N. J., & Collins, A. T. (2004) · Journal of Cell Science · doi:10.1242/jcs.01222 · Cited by 770
Self-citationGrandis, J. R., Drenning, S. D., Zeng, Q., Watkins, S. C., Melhem, M. F., Endo, S., Johnson, D. E., Huang, L., He, Y., & Kim, J. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4227 · Cited by 588
Identification of a Cell of Origin for Human Prostate Cancer
Goldstein, A. S., Huang, J., Guo, C., Garraway, I. P., & Witte, O. N. (2010) · Science · doi:10.1126/science.1189992 · Cited by 552
STAT3 Is Required for Proliferation and Maintenance of Multipotency in Glioblastoma Stem Cells
Sherry, M. M., Reeves, A., Wu, J. K., & Cochran, B. H. (2009) · Stem Cells · doi:10.1002/stem.185 · Cited by 478
Bellido, T., Jilka, R. L., Boyce, B. F., Girasole, G., Broxmeyer, H. E., Dalrymple, S. A., Murray, R., & Manolagas, S. C. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117995 · Cited by 429
Adler, H. L., McCURDY, M. A., Kattan, M. W., Timme, T. L., Scardino, P. T., & Thompson, T. C. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)62092-5 · Cited by 387
Garcia, R., Yu, C., Hudnall, A. M., Catlett, R., Nelson, K. L., Smithgall, T. E., Fujita, D. J., Ethier, S. P., & Jove, R. (1997) · PubMed · Cited by 369
Collins, A. T., Habib, F. K., Maitland, N. J., & Neal, D. E. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.21.3865 · Cited by 357
Self-citationSerum interleukin 6 as a prognostic factor in patients with prostate cancer.
Nakashima, J., Tachibana, M., Horiguchi, Y., Oya, M., Ohigashi, T., Asakura, H., & Murai, M. (2000) · PubMed · Cited by 351
Targeting Interleukin 6 Signaling Suppresses Glioma Stem Cell Survival and Tumor Growth
Wang, H., Lathia, J. D., Wu, Q., Wang, J., Li, Z., Heddleston, J. M., Eyler, C. E., Elderbroom, J. L., Gallagher, J., Schuschu, J., et al. (2009) · Stem Cells · doi:10.1002/stem.188 · Cited by 338
Interleukin-6 Is an Autocrine Growth Factor in Human Prostate Cancer
Giri, D., Özen, M., & Ittmann, M. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63067-2 · Cited by 336
Gouilleux-Gruart, V, Gouilleux, F., Desaint, C., Claisse, J., Capiod, J., Delobel, J., Weber-Nordt, R., Dusanter-Fourt, I., Dreyfus, F., Groner, B., et al. (1996) · Blood · doi:10.1182/blood.v87.5.1692.1692 · Cited by 316
STAT3 Is Necessary for Proliferation and Survival in Colon Cancer–Initiating Cells
Lin, L., Liu, A., Peng, Z., Lin, H.-J. L., Li, P., Li, C., & Lin, J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4660 · Cited by 295
Self-citationBasal epithelial stem cells are efficient targets for prostate cancer initiation
Lawson, D. A., Yang, Z., Memarzadeh, S., Li, X., Huang, J.-T., & Witte, O. (2010) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0913873107 · Cited by 291
Interleukin-6: A candidate mediator of human prostate cancer morbidity
Twillie, D. A., Eisenberger, M. A., Carducci, M. A., Hseih, W.-S., Kim, W. Y., & Simons, J. W. (1995) · Urology · doi:10.1016/s0090-4295(99)80034-x · Cited by 286
Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer
Drachenberg, D., Elgamal, A. A., Rowbotham, R. K., Peterson, M. K., & Murphy, G. P. (1999) · The Prostate · doi:10.1002/(sici)1097-0045(19991001)41:2 · Cited by 282
Interleukin-6 and prostate cancer progression
SMITH, P., Hobisch, A., Lin, D. C., CULIG, Z., & KELLER, E. (2001) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(00)00021-6 · Cited by 268
Photochemical preparation of a pyridone containing tetracycle: A jak protein kinase inhibitor
Thompson, J. E., Cubbon, R. M., Cummings, R. T., Wicker, L. S., Frankshun, R. A., Cunningham, B. R., Cameron, P. M., Meinke, P. T., Liverton, N. J., Weng, Y., et al. (2002) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(02)00106-3 · Cited by 267
Watson, C. J. E., & Miller, W. R. (1995) · British Journal of Cancer · doi:10.1038/bjc.1995.162 · Cited by 226
Dorff, T., Goldman, B., Pinski, J., Mack, P., Lara, P., Veldhuizen, P. V., Quinn, D., Vogelzang, N., Thompson, I., & Hussain, M. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3122 · Cited by 219
Birnie, R., Bryce, S. D., Roome, C., Dussupt, V., Droop, A., Lang, S., Berry, P. A., Hyde, C. F., Lewis, J. L., Stower, M. J., et al. (2008) · Genome biology · doi:10.1186/gb-2008-9-5-r83 · Cited by 212
Self-citationFizazi, K. S., Bono, J. S. D., Fléchon, A., Heidenreich, A., Voog, É., Davis, N. B., Qi, M., Bandekar, R. R., VERMEULEN, J. T., Cornfeld, M. J., et al. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.10.014 · Cited by 198
Lin, L., Hutzen, B. J., Li, P., Ball, S. L., Zuo, M., Deangelis, S., Foust, E., Sobo, M., Friedman, L., Bhasin, D., et al. (2010) · Neoplasia · doi:10.1593/neo.91196 · Cited by 196
Self-citationPedranzini, L., Dechow, T. N., Berishaj, M., Comenzo, R. L., Zhou, P., Azare, J., Bornmann, W. G., & Bromberg, J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4280 · Cited by 150
Garraway, I. P., Sun, W., Tran, C. P., Perner, S., Zhang, B., Goldstein, A. S., Hahm, S. A., Haider, M. A., Head, C. S., Reiter, R. E., et al. (2009) · The Prostate · doi:10.1002/pros.21083 · Cited by 145
Stat3 activation in prostatic carcinomas
Dhir, R., Ni, Z., Lou, W., DeMiguel, F., Grandis, J. R., & Gao, A. C. (2002) · The Prostate · doi:10.1002/pros.10079 · Cited by 136
Hsu, H., Huang, P., Chang, Y., Tzao, C., Chen, Y., Shih, H., Hung, S., Chen, Y., Tseng, L., & Chiou, S. (2011) · Cancer · doi:10.1002/cncr.25869 · Cited by 113
Cavarretta, I. T. R., Neuwirt, H., Untergasser, G., Moser, P. L., Zaki, M. H., Steiner, H., Rumpold, H. F., Fuchs, D., Hobisch, A., Nemeth, J. A., et al. (2006) · Oncogene · doi:10.1038/sj.onc.1210097 · Cited by 105
Analysis of Signal Transducer and Activator of Transcription 3 (Stat 3) Pathway in Multiple Myeloma
Quintanilla-Martinez, L., Kremer, M., Specht, K., Calzada-Wack, J., Nathrath, M., Schaich, R., Höfler, H., & Fend, F. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64278-2 · Cited by 93
Lin, L., Benson, D. M., DeAngelis, S., Bakan, C. E., Li, P., Li, C., & Lin, J. (2012) · International Journal of Cancer · doi:10.1002/ijc.26152 · Cited by 66
Self-citationSteiner, H., Cavarretta, I. T. R., Moser, P. L., Berger, A. P., Bektić, J., Dietrich, H., Zaki, M. H., Nakada, M. T., Hobisch, A., Nemeth, J. A., et al. (2006) · The Prostate · doi:10.1002/pros.20492 · Cited by 39
Brehm, M. A., Mangada, J., Markees, T. G., Pearson, T., Daniels, K. A., Thornley, T. B., Welsh, R. M., Rossini, A. A., & Greiner, D. L. (2006) · Blood · doi:10.1182/blood-2006-03-008219 · Cited by 29
(2003) · PubMed
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Pattabiraman, D. R., & Weinberg, R. A. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4253 · Cited by 1,013
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Metadata
- 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)
- Venue
- Cancer Research
- Published
- 2013-08-13
- Volume
- 73
- Issue
- 16
- Pages
- 5288-5298
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- 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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