The DOI matches its Crossref record; 31 of the 35 references it cites were found in a registry or an index.
Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis.
Abstract
Objectives Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy.Methods Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone.Results Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P <0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P </=0.041), prostatectomy tumor volume (P </=0.048), and final Gleason sum (P </=0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P </=0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P </=0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P </=0.042).Conclusions Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
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“The levels of IL-6 and its soluble receptor, IL-6sR, in circulating plasma is increased in patients with aggressive metastatic disease and can be predictive of recurrence after treatment of localized cancer (17).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [17]
Citations
Cites
Natural History of Progression After PSA Elevation Following Radical Prostatectomy
Pound, C. R. (1999) · JAMA · doi:10.1001/jama.281.17.1591 · Cited by 3,077
A Preoperative Nomogram for Disease Recurrence Following Radical Prostatectomy for Prostate Cancer
Kattan, M. W., Eastham, J. A., Stapleton, A. M. F., Wheeler, T. M., & Scardino, P. T. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.10.766 · Cited by 1,243
IL-6 is produced by osteoblasts and induces bone resorption.
Ishimi, Y., Miyaura, C., Jin, C., Akatsu, T., Abe, E., Nakamura, Y. K., Yamaguchi, A., Yoshiki, S., Matsuda, T., Hirano, T., et al. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.10.3297 · Cited by 1,128
Soluble receptors for cytokines and growth factors: generation and biological function
Rose‐John, S., & Heinrich, P. C. (1994) · Biochemical Journal · doi:10.1042/bj3000281 · Cited by 777
Evidence for the involvement of interleukin 6 in experimental cancer cachexia.
Strassmann, G., Fong, M., Kenney, J. S., & Jacob, C. O. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115767 · Cited by 660
Prediction of Progression Following Radical Prostatectomy
Epstein, J. I., Partin, A. W., Sauvageot, J., & Walsh, P. C. (1996) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199603000-00004 · Cited by 560
Hobisch, A., Eder, I. E., Putz, T., Horninger, W., Bartsch, G. C., Klocker, H., & Čulig, Z. (1998) · PubMed · Cited by 437
Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma.
Blay, J., Négrier, S., Combaret, V., Attali, S., Goillot, E., Merrouche, Y., Mercatello, A., Ravault, A., Tourani, J. M., & Jf, M. (1992) · PubMed · Cited by 420
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
Serum 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
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Imayama, I., Mason, C. E., & Duggan, C. R. (2010) · Springer eBooks · doi:10.1007/978-1-4419-7551-5_6 · Cited by 3
Coutant, D. E., Rehmel, J., Edwards, D. M., & Hall, S. D. (2025) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-025-03839-1 · Cited by 2
“…mean circulating IL-6 concentrations were high in patients with prostate cancer metastatic to bone (47.4 ± 21.3 pg/mL, n = 20), but IL-6 concentrations in non-meta-static prostate cancer patients (2.5 ± 1.6 pg/mL, n = 19) did not separate from healthy control values (1.9 ± 0.6 pg/mL, n = 44) [26].”
InfluentialKrishna, M., Garg, P., Horne, D. A., Salgia, R., & Singhal, S. S. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218647 · Cited by 3
Ibrahim, A. S., Farrag, W. S., & Aly, M. G. (2018) · Egyptian Journal of Anaesthesia · doi:10.1016/j.egja.2018.07.003 · Cited by 2
“Both IL-6 and TNF-a, with same biological properties, and concerned in the development of cancer prostate [9].”
BackgroundNagahara, A., Uemura, M., Sato, M., Nakata, W., Tsujihata, M., Takao, T., Matsumura, S., Nishimura, K., Takada, S., Iwanishi, T., et al. (2024) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyae004 · Cited by 2
“It was previously reported that IL-6 in the serum of prostate cancer patients is elevated both in metastatic prostate cancer patients (12,13) and in CRPC patients (14,15).”
BackgroundContribution of osteoclasts to the bone–tumor niche
Edwards, J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-416721-6.00005-4 · Cited by 2
Molecular biomarkers in prostate cancer
Martínez, C. H., Chalasani, V., & Chin, J. L. (2009) · Expert Opinion on Medical Diagnostics · doi:10.1517/17530050902893303 · Cited by 2
“Multiple studies have shown that serum levels of IL-6 and its ligand-specific soluble receptor (IL-6sR) are elevated in patients with prostate cancer, and are correlated with prognosis [62-65].”
BackgroundThe Role of Androgen Receptor in Prostate Cancer
Berger, A., & Rickman, D. S. (2017) · Molecular pathology library · doi:10.1007/978-3-319-64096-9_20 · Cited by 2
MİDE KANSERİ HASTALARINDA PERİFERİK KAN SAYIMI İLE PROGNOZ ARASINDAKİ İLİŞKİ
Okuyucu, M., & Yücel, İ. (2019) · Journal of Istanbul Faculty of Medicine / İstanbul Tıp Fakültesi Dergisi · doi:10.26650/iuitfd.2018.0014 · Cited by 2
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BackgroundRole of IL-6 in Regulating the Androgen Receptor
Čulig, Z., & Hobisch, A. (2009) · Springer eBooks · doi:10.1007/978-0-387-69179-4_20 · Cited by 2
“Interestingly, the presence of the soluble receptor in prostate cancer tissue specimens has been associated with poor prognosis (Shariat et al. 2001).”
BackgroundAlternative Tests to Psa for Prostate Cancer Diagnosis
Defilippi, E., Zitella, A., & Tizzani, A. (2011) · Urologia Journal · doi:10.5301/ru.2011.7973 · Cited by 1
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Wang, L. C., Scherr, D. S., & Shariat, S. F. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-188-2_7 · Cited by 1
Development of Novel Assays for Measuring Different Molecular Forms of Prostate Specific Antigen
Zhu, L. (2009) · Työväentutkimus Vuosikirja · Cited by 1
Hałaś, A. (2010) · Publication Server of Kaiserslautern University of Technology (Kaiserslautern University of Technology)
Tawara, K. (2011) · ScholarWorks (Boise State University)
Wu, M. (2005) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/3tqd-h450
Accelerated Tumor Cell Death by Angiogenic Modifiers
Chung, L. W. K., Hsieh, C., Bradley, M., & Sokoloff, M. H. (2001) · Defense Technical Information Center (DTIC) · doi:10.21236/ada403672
Herring, P. A., Ingels, J. F., Carbone, L. D., Barrow, K. D., Osborn, D., Dietzen, D. J., & Pifer, L. L. W. (2003) · Journal of Environmental Pathology Toxicology and Oncology · doi:10.1615/jenvironpatholtoxicoloncol.v22.i2.80
Shariat, S. F., Walz, J. C., Roehrborn, C. G., Montorsi, F., Claudio Jeldres, A., Fred Saad, C., Slawin, K. M., & Karakiewicz, P. I. (2008) · The Journal of Urology · doi:10.1016/s0022-5347(08)60161-5
Sharifi, N., Hurt, E. M., Thomas, S., & Farrar, W. L. (2008) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(08)72094-9
Prostate cancer : Aspects of screening and prognostic factors
Kjellman, A. (2010) · Figshare
Roman, L. N. (2006) · D-Scholarship@Pitt (University of Pittsburgh)
Appenteng, K. (2009) · D-Scholarship@Pitt (University of Pittsburgh)
Review Tumor metastasis to bone
Virk, M. S., & Lieberman, J. R. (2007)
Review TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate
Royuela, M., Rodríguez‐Berriguete, G., Fraile, B., & Paniagua, R. (2008)
Use of Quercetin in Prostate Cancer Cell
Young, C. Y. F. (2009) · Beer in Health and Disease Prevention · doi:10.1016/b978-0-12-373891-2.00088-2
Biomarkers of Potential Therapeutic Value
Miyake, H., Takenaka, A., & Fujisawa, M. (2012) · Springer eBooks · doi:10.1007/978-1-4471-2864-9_15
Turning data into decisions : clinical decision support in orthopaedic oncology
Forsberg, J. A. (2015) · Figshare
Liu, C., Zhu, Y., Lou, W., Cui, Y., Evans, C. P., & Gao, A. C. (2014) · The Journal of Urology · doi:10.1016/j.juro.2014.02.289
Mwirigi, L. K. (2015) · Kenyatta University Institutional Repository (Kenyatta University)
Identification of new urine biomarkers for the detection of prostate cancer
Rigau, M. (2011) · TDX (Tesis Doctorals en Xarxa)
Skaar, D. A., Jirtle, R. L., & Hoyo, C. (2016) · Energy balance and cancer · doi:10.1007/978-3-319-41610-6_5
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Rathinavelu, A., & Levy, A. (2016) · InTech eBooks · doi:10.5772/64337
Sardana, G. (2008) · TSpace (University of Toronto)
Biomarcatori emergenti per la diagnosi e la valutazione prognostica del carcinoma della prostata
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Targeting Neuromimicry in Prostate Cancer Metastasis
Wu, B. J. (2016)
Review Article Metabolic imbalance and prostate cancer progression
Burton, A. J., Tilling, K. M., Holly, J. M. P., Hamdy, F. C., Rowlands, M., & Martin, R. M. (2010)
Adipokines and Prostate Cancer
Thompson, C. L., & Reece, M. (2017) · Energy balance and cancer · doi:10.1007/978-3-319-64940-5_4
Данилець, Р. О. (2017) · Health of Man · doi:10.30841/2307-5090.2(61).2017.116015
Three Dimensional Prostate Cancer Model Systems
Mosaad, E. M. O. (2018) · Queensland University of Technology · doi:10.5204/thesis.eprints.118287
Albayrak, A. T., & Şerefoğlu, E. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816665-9.00007-x
Androgen metabolism in castration-resistant prostate cancer
Koltai, T., Reshkin, S. J., Baltazar, F., & Fliegel, L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-90528-2.00003-5
Aminuddin, A., Masre, S. F., Teow, S., & Ng, P. Y. (2021) · Springer eBooks · doi:10.1007/978-981-33-6827-9_8
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Hernández, J., Canby‐Hagino, E., & Thompson, I. M. (2005) · Current Prostate Reports · doi:10.1007/s11918-005-0003-7
“Various investigators have demonstrated elevated plasma levels of transforming growth factor β1 (TGF β1), interleukin (IL)-6, and the soluble form of its receptor (IL-6sR) in patients with metastatic prostate cancer [ 65 ,66].”
BackgroundYoon, Y., Liang, Z., Zhang, X., Choe, M., Zhu, A., Cho, H. T., Shin, D. M., Goodman, M. M., Chen, Z. (., & Shim, H. (2023) · doi:10.1158/0008-5472.c.6494897
Yoon, Y., Liang, Z., Zhang, X., Choe, M., Zhu, A., Cho, H. T., Shin, D. M., Goodman, M. M., Chen, Z. (., & Shim, H. (2023) · doi:10.1158/0008-5472.c.6494897.v1
Nagahara, A., Uemura, M., Sato, M., Nakata, W., Tsujihata, M., Takao, T., Matsumura, S., Nishimura, K., Takada, S., Iwanishi, T., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3289099/v1
Das, S., & Ghosh, A. (2024) · Springer eBooks · doi:10.1007/978-981-96-0301-5_1
Obesogens in Prostate Cancer: An Endocrine and Metabolic Threat
Feijó, M., Fonseca, L. R. S., Kiss‐Toth, E., Socorro, S., & Correia, S. T. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00690-y
“Moreover, elevated IL-6 levels have been associated with bone metastases and shorter survival times [363, 364].”
The Role of the Tumor Microenvironment in the Pathophysiology of Urological Cancers
Kakelia, M., Saini, A. K., Saini, R. V., & Saboor, M. (2026) · Springer eBooks · doi:10.1007/978-981-92-1158-6_2
Obesity-Related Male Sexual Dysfunction: Pathophysiology and Clinical Implications
Albayrak, A. T. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1017181
Metadata
- Authors
- Shariat, S. F., Andrews, B., Kattan, M. W., Kim, J., Wheeler, T. M., & Slawin, K. M.
- Affiliations
- Houston Methodist (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Slawin, Kevin M.
- Venue
- Urology
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 58
- Issue
- 6
- Pages
- 1008-1015
- ISSN
- 0090-4295 (ISSN-L)
- OpenAlex
- W2009017218
- Cited by
- 261
- References
- 35
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 17 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 9 · 2016: 9 · 2015: 19 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Urology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1p20ca058203-01)
- National Cancer Institute (CA58203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
- Keywords
- interleukin-6, soluble IL-6 receptor, prostate cancer, bone metastasis, biochemical recurrence, radical prostatectomy, prognostic factors, Gleason score, prostate-specific antigen, tumor progression, gp130 signaling
- MeSH terms
- Adult, Aged, Analysis of Variance, Biopsy, Bone Neoplasms, Follow-Up Studies, Humans, Male, Middle Aged, Prostate, Prostatectomy, Prostatic Neoplasms, Biomarkers, Tumor, Interleukin-6, Proportional Hazards Models, Disease Progression, Receptors, Interleukin-6
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