Interleukin-6, tumour necrosis factor α and interleukin-1β in patients with renal cell carcinoma

Yoshida, Naomasa; Ikemoto, Shinichi; Narita, Keisuke; Sugimura, Kazunobu; Wada, Seiji; Yasumoto, R; Kishimoto, Toshifumi; Nakatani, Tatsuya

doi:10.1038/sj.bjc.6600257

Cited by 162 publications

(99 citation statements)

References 18 publications

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“…In a series of 122 patients with renal cell carcinoma, Yoshida et al (2002) demonstrated that serum levels of TNF-a directly correlated with advanced stage grouping as compared with controls, and suggested that TNF-a could be useful in the early diagnosis of the disease. There has been a single study by Nakashima et al (1998), where TNF-a has been shown to be associated with prostate cancer progression.…”

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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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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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“…In RCC, inflammatory reactions are correlated with a poor patient prognosis. The serum levels of TNF-a are significantly higher and correlated with tumor size in RCC (7,8). In addition, infliximab, a chimeric anti-human TNFa antibody, was effective in the therapy of RCC patients in 2 phase II studies (8).…”

Section: Introductionmentioning

confidence: 97%

TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism

Tang

Chuang

et al. 2012

Molecular Cancer Research

107

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TNF-a is a cytokine with antitumorigenic property. In contrast, low dose, chronic TNF-a production by tumor cells or stromal cells may promote tumor growth and metastasis. Serum levels of TNF-a are significantly elevated in renal cell carcinoma (RCC) patients. Here, we showed that TNF-a induced epithelial-mesenchymal transition (EMT) and promoted tumorigenicity of RCC by repressing E-cadherin, upregulating vimentin, activating MMP9, and invasion activities. In addition, TNF-a treatment inhibited glycogen synthase kinase 3b (GSK-3b) activity through serine-9 phosphorylation mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway in RCC cells. Inhibition of PI3K/AKT by LY294002 reactivated GSK-3b and suppressed the TNFa-induced EMT of RCC cells. Inactivation of GSK-3b by LiCl significantly increased MMP9 activity and EMT of RCC cells. Activation of GSK-3b by transduction of constitutively active GSK-3b into RCC cells suppressed TNFa-mediated anchorage-independent growth in soft agar and tumorigenicity in nude mice. Overexpression of a kinase-deficient GSK-3b, in contrast, potentiated EMT, anchorage-independent growth and drastically enhanced tumorigenicity in vivo. Most importantly, a 15-fold inactivation of GSK-3b activity, 3-fold decrease of E-cadherin, and 2-fold increase of vimentin were observed in human RCC tumor tissues. These results indicated that inactivation of GSK-3b plays a pivotal role in the TNF-a-mediated tumorigenesis of RCC. Mol Cancer Res; 10(8); 1109-19. Ó2012 AACR. IntroductionRenal cell carcinoma (RCC) is the tenth most common cause of cancer-related deaths worldwide (1). Although surgery is often curative, 30% of patients will present with metastases at the time of initial diagnosis (1). The 5-year survival rate is only 5% in metastatic RCC as advanced RCC is resistant to chemotherapy and radiotherapy (2, 3). Previous studies indicated immunotherapy is relatively effective against RCC (2, 3). However, the response rate is only 15% to 20% (1-3). Therefore, defining the factors involved in disease progression and metastasis will provide novel molecular targets for the development of effective therapies.

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“…In patients with RCC, plasma TNF-a is significantly higher and associated with tumor size, grade, and stage. 22 Therefore, we sought to determine whether Gal-1 was involved in the transcriptional upregulation of CXCR4 induced by TNF-a. As shown in Figure 5, A and B, TNF-a increased protein levels of Gal-1 and CXCR4 and induced CXCR4 promoter activity in shLuc-or shLacZ-infected A-498 control cells.…”

Section: Gal-1 Promoted Cell Motility and Clonogenicity Of Rcc Cells mentioning

confidence: 99%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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Galectin-1, a b-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-kB (NF-kB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-kB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease. 25: 148625: -149525: , 201425: . doi: 10.1681 Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies. 1 More than one third of patients will present with locally advanced or metastatic disease at the time of diagnosis. 2 The 5-year survival rate of metastatic RCC is only 10% because of resistance to chemotherapy and radiation therapy. 3 Although cytokine therapy with IFN-a and IL-2 is the gold standard treatment, its overall efficacy rate is limited by its significant toxicity. 4 Recently, several molecular targeting drugs, including sunitinib and temsirolimus, have been approved for advanced RCC. 4 However, treatment response is not long-standing and overall survival remains poor. Thus, the identification of novel molecular targets in RCC is urgently needed for the development of effective therapies. J Am Soc Nephrol

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Interleukin-6, tumour necrosis factor α and interleukin-1β in patients with renal cell carcinoma

Cited by 162 publications

References 18 publications

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

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

TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

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