Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis

Shariat, Shahrokh F.; Andrews, Ben; Kattan, Michael W.; Kim, JaHong; Wheeler, Thomas M.; Slawin, Kevin M.

doi:10.1016/s0090-4295(01)01405-4

Cited by 226 publications

(161 citation statements)

References 27 publications

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“…Several etiologic factors have been proposed involving a broad range of molecular systems, pathways, and mechanisms. Adipokines, markers of immune response, metalloproteinases, adhesion molecules, hormones, and several growth factors have been implicated in the process of both cancer initiation and progression in the prostate as well as in other organ systems (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Several from these groups have been proposed as biomarkers for cancer detection as well as for prognosis and follow-up in prostate cancer based on their detection in different biospecimens (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Parekh¹,

Ankerst²,

Baillargeon³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: We analyzed the association of 54 biomarkers from seven classes including adipokines, immune response metalloproteinases, adhesion molecules, and growth factors with prostate cancer risk adjusting for the Prostate Cancer Prevention Trial (PCPT) risk score. Methods: A total of 123 incident prostate cancer cases and 127 age-matched controls were selected from subjects in the San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. Prediagnostic serum concentrations were measured in the sample collected at baseline using LabMAP technology. The odds ratios (OR) of prostate cancer risk associated with serum concentrations of 54 markers were estimated using univariate conditional logistic regression before and after adjustment for the PCPT risk score. Two-way hierarchical unsupervised clustering techniques were used to evaluate whether the 54-marker panel distinguished cases from controls. Results: Vascular endothelial growth factor, resistin, interleukin 1Ra (IL-1Ra), granulocyte colony-stimulating factor, matrix metalloproteinase-3, plasminogen activator inhibitor, and kallikrein-8 were statistically significantly (P < 0.05) underexpressed in prostate cancer cases, and A-fetoprotein was statistically significantly overexpressed in prostate cancer cases, but all had area underneath the receiver-operating characteristic curve <60%; none were statistically significant adjusting for multiple comparisons (P < 0.0008) or after adjustment for the PCPT risk score. Statistical clustering of patients by the marker panel did not distinguish a separate group of cases from controls. Conclusions: This age-matched case-control study did not support findings of increased diagnostic potential from a 54-marker panel when compared with the conventional risk factors incorporated in the PCPT risk calculator. Future discovery of new biomarkers should always be tested and compared against conventional risk factors before applying them in clinical practice. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1966 -72)

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Section: Introductionmentioning

confidence: 99%

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Parekh¹,

Ankerst²,

Baillargeon³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Surprisingly perhaps for a tumour where there is such clear evidence of a primary hormonal basis to its development, there is emerging evidence of cytokine involvement. IL-6 and TNF-a, two cytokines with multiple and overlapping biological properties, are involved in prostate cancer development (Shariat et al, 2001;Smith et al, 2001).…”

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confidence: 99%

Serum levels of IL-6 and TNF-α correlate with clinicopathological features and patient survival in patients with prostate cancer

et al. 2004

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Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-a) are important multifunctional cytokines involved in tumour growth and metastasis. In this study, we have measured serial levels of serum IL-6 and TNF-a in prostate cancer patients. A total of 80 patients with carcinoma of the prostate and 38 controls were studied. Three patient groups, with small bulk localised, large volume localised and metastatic prostate cancer, were assessed. Serum IL-6 and TNF-a levels were measured and correlated with clinicopathological variables and patient survival. Serial changes in these cytokines were also assessed and related to disease progression in 40 patients with recurrent prostate cancer. Serum IL-6 levels in patients with metastatic disease (9.377.8 pg ml À1 ) were higher than those in patients with localised disease (1.370.8 pg ml À1 , Po0.001). Significantly elevated levels of TNF-a were found in metastatic disease (6.373.6 pg ml À1 ) compared with localised disease (1.170.5 pg ml À1 , Po0.001). The levels of both cytokines were directly correlated with the extent of the disease. Serial analysis in 40 patients with recurrent tumours showed that both cytokines became elevated at the point of prostate-specific antigen progression. In conclusion, these results suggest that IL-6 and TNF-a correlate with the extent of disease in patients with prostate cancer and may be monitored in conjunction with other disease markers.

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“…IL6 activates AR in a STAT3-dependent manner, while antibodies to IL6 reverse castration resistance (Lee et al 2003, Wallner et al 2006. Furthermore, levels of IL6R are predictive of biochemical recurrence of prostate cancer and metastasis (Shariat et al 2001, Kattan et al 2003. Thus, SOD2 repression is found to contribute to castration resistance via AR reactivation by several mechanisms.…”

Section: Effects Of Oxidative Stress On Ar Signalingmentioning

confidence: 99%

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

Shiota

Yokomizo

Naito

2012

Endocrine-Related Cancer

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Oxidative stress caused by an increase in reactive oxygen species levels or a decrease in cellular antioxidant capacity can evoke the modulation of various cellular events including androgen receptor (AR) signaling via direct or indirect interactions. In this review, we summarize the mechanisms of AR activation by oxidative stress including: i) AR overexpression; ii) AR activation by AR co-regulators or intracellular signal transduction pathways; iii) generation of AR mutations or splice variants; and iv) de novo androgen synthesis. AR signaling augmented by oxidative stress appears to contribute to pro-survival and anti-apoptotic effects in prostate cancer cells in response to androgen deprivation therapy. In addition, AR signaling suppresses anti-survival and pro-apoptotic effects in prostate cancer cells in response to various cytotoxic and tumorsuppressive interventions including taxanes and radiation through the modulation of bIII-tubulin and ataxia telangiectasia-mutated kinase expression respectively. Taken together, AR signaling appears to render prostate cancer cells refractory to various therapeutic interventions including castration, taxanes, and radiation, indicating that AR signaling is a comprehensive resistant factor and crucial target for prostate cancer treatment.

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Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis

Cited by 226 publications

References 27 publications

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Serum levels of IL-6 and TNF-α correlate with clinicopathological features and patient survival in patients with prostate cancer

Pro-survival and anti-apoptotic properties of androgen receptor signaling by oxidative stress promote treatment resistance in prostate cancer

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