IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity

Kryczek, Ilona; Gryboś, Marian; Karabon, Lidia; Klimczak, Aleksandra; Lange, Andrzej

doi:10.1054/bjoc.1999.0973

Cited by 38 publications

(28 citation statements)

References 24 publications

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“…High interleukin-6 (IL-6) levels in the ascitic fluid of ovarian cancer patients were correlated with poor prognosis (6). Other studies have highlighted the crucial role of IL-6 in the pathogenesis of ovarian cancer (54,55). In the present study, we found significantly higher levels of macrophage chemoattractant protein-1 (MCP-1; >2.5-fold) in SP À/À ascitic fluid (Fig.…”

Section: Sparc Ameliorates the Peritoneal Tumor -Induced Inflammationsupporting

confidence: 64%

Normalization of the Ovarian Cancer Microenvironment by SPARC

Said¹,

Socha²,

Olearczyk³

et al. 2007

Molecular Cancer Research

102

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Section: Sparc Ameliorates the Peritoneal Tumor -Induced Inflammationsupporting

confidence: 64%

Normalization of the Ovarian Cancer Microenvironment by SPARC

Said¹,

Socha²,

Olearczyk³

et al. 2007

Molecular Cancer Research

102

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“…Other cytokines that may have a significant effect on the composition of the tumour-infiltrating lymphocyte pool are TGFb and IL-6, which have both been found in abundance in a variety of tumours, particularly advanced tumours (Asselin-Paturel et al, 1998;Conrad et al, 1999;Kryczek et al, 2000). IL-6 recently emerged as a major player governing the differentiation of naive T cells.…”

Section: Inducible Tregsmentioning

confidence: 99%

Positive and negative influences of regulatory T cells on tumour immunity

Gallimore

Simon

2008

Oncogene

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Clinicians and scientists have long questioned whether the immune system has a role in destroying cancerous tissue. Studies performed in animal models have, however, recently revealed that the immune system can, at least in principle, effectively control tumours. In parallel with these findings, a large body of evidence indicates that although the immune system has the capacity to control tumours, there are also regulatory mechanisms that subdue these responses. A major challenge of tumour immunotherapy, therefore, is to find ways of disabling these regulatory functions while restoring or priming any immune responses that are protective.

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“…EOC cells in vitro have also been demonstrated to modulate the macrophage phenotype by inducing the expression of inflammatory mediators (Hagemann et al, 2005). Among the cyto/ chemokines found in EOC ascites, IL-6 has been shown to be a growth-promoting and anti-apoptotic factor (Kryczek et al, 2000). Moreover, patients with high levels of IL-6 expression have shorter survival than patients with lower levels (Penson et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Ligand-dependent EGFR activation induces the co-expression of IL-6 and PAI-1 via the NFkB pathway in advanced-stage epithelial ovarian cancer

et al. 2011

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The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, is expressed in up to 70% of epithelial ovarian cancers (EOCs), where it correlates with poor prognosis. The majority of EOCs are diagnosed at an advanced stage, and at least 50% present malignant ascites. High levels of IL-6 have been found in the ascites of EOC patients and correlate with shorter survival. Herein, we investigated the signaling cascade led by EGFR activation in EOC and assessed whether EGFR activation could induce an EOC microenvironment characterized by pro-inflammatory molecules. In vitro analysis of EOC cell lines revealed that ligand-stimulated EGFR activated NFkB-dependent transcription and induced secretion of IL-6 and plasminogen activator inhibitor (PAI-1). IL-6/PAI-1 expression and secretion were strongly inhibited by the tyrosine kinase inhibitor AG1478 and EGFR silencing. A significant reduction of EGF-stimulated IL-6/PAI-1 secretion was also obtained with the NFkB inhibitor dehydroxymethylepoxyquinomicin. Of 23 primary EOC tumors from advanced-stage patients with malignant ascites at surgery, 12 co-expressed membrane EGFR, IL-6 and PAI-1 by immunohistochemistry; both IL-6 and PAI-1 were present in 83% of the corresponding ascites. Analysis of a publicly available gene-expression data set from 204 EOCs confirmed a significant correlation between IL-6 and PAI-1 expression, and patients with the highest IL-6 and PAI-1 co-expression showed a significantly shorter progression-free survival time (P ¼ 0.028). This suggests that EGFR/NFkB/IL-6-PAI-1 may have a significant impact on the therapy of a particular subset of EOC, and that IL-6/PAI-1 co-expression may be a novel prognostic marker.

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IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity

Cited by 38 publications

References 24 publications

Normalization of the Ovarian Cancer Microenvironment by SPARC

Normalization of the Ovarian Cancer Microenvironment by SPARC

Positive and negative influences of regulatory T cells on tumour immunity

Ligand-dependent EGFR activation induces the co-expression of IL-6 and PAI-1 via the NFkB pathway in advanced-stage epithelial ovarian cancer

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