Serum Cytokine Profiling as a Diagnostic and Prognostic Tool in Ovarian Cancer: A Potential Role for Interleukin 7

Lambeck, Annechien J. A.; Crijns, Anne; Leffers, Ninke; Sluiter, Wim J.; Hoor, Klaske A. ten; Braid, Mike; Zee, Ate G.J. van der; Daemen, Toos; Nijman, Hans W.; Kast, W. Martin

doi:10.1158/1078-0432.ccr-06-1828

Cited by 96 publications

(93 citation statements)

References 17 publications

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“…In ovarian cancer, IL7 acts as a growth factor, like in breast cancer, and has been found in ascites and plasma 39,94,95 . pDcs are also present in tumor environment and stimulate tumor growth by releasing TNF-α and IL8.…”

Section: Proteins Associated With Cell Proliferationmentioning

confidence: 99%

MALDI-MSI and Ovarian Cancer Biomarkers

Longuespée

Boyon²,

Kerdraon³

et al. 2012

Advances in Cancer Management

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Section: Proteins Associated With Cell Proliferationmentioning

confidence: 99%

MALDI-MSI and Ovarian Cancer Biomarkers

Longuespée

Boyon²,

Kerdraon³

et al. 2012

Advances in Cancer Management

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“…Some of these cytokines have been considered as serologic biomarkers of EOC (11). Among them, interleukin (IL)-18 was proposed as a potential biomarker by gene expression profiling (12) and, indeed, IL-18 levels were elevated in serum and ascites of patients with EOC (12,13).…”

Section: Introductionmentioning

confidence: 99%

The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment

Carbotti

Barisione

Orengo

et al. 2013

Clinical Cancer Research

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Purpose: Interleukin (IL)-18 is an immune-enhancing cytokine, which induces IFN-g production, T-helper 1 responses, and antitumor effects. In turn, IFN-g stimulates IL-18-binding protein production, which blocks IL-18 activity. In view of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy, here, we studied IL-18BP expression and its regulation by cytokines in EOC cells in vitro and in vivo.Experimental Design: Expression and production of IL-18BP in EOC cell lines, primary ovarian carcinomas, and the corresponding normal tissues, patients' serum, and ascites were investigated by immunochemistry, ELISA, screening of gene expression profiles, and reverse-transcription PCR.Results: Analysis of gene expression profiles revealed that IL18BP mRNA is increased in EOC tumors compared with normal ovary cells. Release of IL-18BP was detectable in EOC sera and to a greater extent in the ascites, indicating production at the tumor site. Indeed, immunochemical analyses on cells isolated from the ascites and on tumor sections indicated that IL-18BP is expressed in both tumor cells and tumor-associated leukocytes, which displayed a CD3 À CD20EOC cell lines do not constitutively express IL-18BP. However, its release is inducible both by IFN-g stimulation in vitro and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a role for the microenvironment. In vitro experiments and immunochemistry indicated that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary cells through STAT1 activation. Together, these data indicate that IL-18BP, which is produced in EOC in response to microenvironmental factors, may inhibit endogenous or exogenous IL-18 activity.

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“…Factors explored as potential serum markers of ovarian cancer include insulin-like growth factor binding protein-2 (Baron- Hay et al 2004), interleukin 7 (IL7; Lambeck et al 2007) and more recently, the combined use of b 2 -microglobulin, apolipoprotein A-1, transthyretin, and transferrin with CA-125, significantly improving the detection of early stage ovarian cancer (Kozak et al 2005, Nosov et al 2009, Fung 2010). This has led to development of the FDA-approved Ovarian Tumour Triage Test, known as OVA1 (Vermillion, Fremont, CA, USA), which is recommended for use in conjunction with imaging and physical examination, but not as an isolated diagnostic test (Fung 2010).…”

Section: Introductionmentioning

confidence: 99%

The chemokine CXCL1 induces proliferation in epithelial ovarian cancer cells by transactivation of the epidermal growth factor receptor

Bolitho

Hahn²,

Baxter³

et al. 2010

Endocrine-Related Cancer

112

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The chemokine CXCL1 is elevated in plasma and ascites from patients with ovarian cancer. We have previously shown that CXCL1 is a marker of phosphatidylinositol 3-kinase signalling in epithelial ovarian cancer (EOC) cell lines, a pathway that is commonly activated in ovarian tumours. To investigate whether CXCL1 also has functional significance in ovarian cancer, this chemokine was either down-regulated using siRNAs or overexpressed by transfection of CXCL1 into the EOC cell lines SKOV3 and OVCAR-3 and proliferation assessed over 7 days. Overexpression of CXCL1 increased proliferation of ovarian cancer cells over 7 days, while down-regulation was inhibitory. Treatment of cells with recombinant CXCL1 induced epidermal growth factor receptor (EGFR) phosphorylation at Y1068, indicating crosstalk between the CXCL1 G-protein-coupled receptor CXCR2 and the EGFR. CXCL1-induced proliferation was also decreased by inhibition of EGFR kinase activity and was dependent on extracellular matrix metalloproteinase-mediated release of heparin-binding EGF (HB-EGF). Involvement of mitogenactivated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signalling was also evident since inhibition of both Ras and MEK activity decreased CXCL1-induced proliferation. CXCL1-induced ERK1/2 phosphorylation was inhibited by the MEK1 inhibitor PD98059; however, EGFR phosphorylation was unaffected, indicating that CXCL1 activation of MAPK signalling is downstream of the EGFR. Taken together, these data show that CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of EOC cells.

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Serum Cytokine Profiling as a Diagnostic and Prognostic Tool in Ovarian Cancer: A Potential Role for Interleukin 7

Cited by 96 publications

References 17 publications

MALDI-MSI and Ovarian Cancer Biomarkers

MALDI-MSI and Ovarian Cancer Biomarkers

The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment

The chemokine CXCL1 induces proliferation in epithelial ovarian cancer cells by transactivation of the epidermal growth factor receptor

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