Interleukin-6 gene amplification and shortened survival in glioblastoma patients

Tchirkov, Andréï; Khalil, T.; Chautard, Emmanuel; Mokhtari, Karima; Véronèse, Lauren; Irthum, B.; Vago, Philippe; Jl, Kémény; Verrelle, Pierre

doi:10.1038/sj.bjc.6603586

Cited by 123 publications

(84 citation statements)

References 11 publications

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“…15,65 Glioma IL-6 expression in glioma has been correlated with tumor grade and vascularity. 66,67 In a recent study, IL-6 gene amplification was observed in patients with glioblastoma who had the most malignant tumors, and IL-6 gene amplification was associated with decreased survival. 66 IL-6 also can serve as an autocrine growth factor and seems to be required for glioma and spontaneous astrocytoma development in mouse models.…”

Section: Translational Correlationsmentioning

confidence: 99%

“…66,67 In a recent study, IL-6 gene amplification was observed in patients with glioblastoma who had the most malignant tumors, and IL-6 gene amplification was associated with decreased survival. 66 IL-6 also can serve as an autocrine growth factor and seems to be required for glioma and spontaneous astrocytoma development in mouse models. 68 Although it remains unknown exactly how IL-6 contributes to the malignant progression of gliomas, IL-6 up-regulates VEGF promoter activity and VEGF protein secretion in glioblastoma cells through activation of STAT3.…”

Section: Translational Correlationsmentioning

confidence: 99%

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Interleukin‐6 and its receptor in cancer

Hong

Angelo

Kurzrock

2007

Cancer

343

127

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Interleukin-6 (IL-6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL-6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL-6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL-6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL-6 are observed in almost every type of tumor studied and predict a poor outcome.

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Section: Translational Correlationsmentioning

confidence: 99%

Section: Translational Correlationsmentioning

confidence: 99%

Interleukin‐6 and its receptor in cancer

Hong

Angelo

Kurzrock

2007

Cancer

343

127

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“…Recently, some studies have shown that IL-6 directly influences the invasiveness of colorectal, head and neck cancers (8,9). In GBM, the autocrine regulation of IL-6 has been recognized since 1990 (10), and its aberrant expression and secretion have been found to be associated with GBM formation (11), angiogenesis, grade (12) and prognosis (13,14). However, the role of IL-6 in the malignant progression of GBM remains unclear (7).…”

Section: Introductionmentioning

confidence: 99%

IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1

Li²,

Deng³

et al. 2010

Oncol Rep

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Abstract. Invasion into adjacent brain parenchyma is the key cause of recurrent human glioblastoma multiforme (GBM). The role of interleukin 6 (IL-6) in the malignant progression of glioma remains undefined. Here, we found that IL-6 promotes the invasion of U87 MG human glioma cells but not in U343 cells. An advanced level of STAT3 activity, and increased expression and secretion of MMP-2, induced by IL-6 in U87 MG cells were observed. Blocking the STAT3 pathway with specific inhibitors of STAT3, JSI-124 or small interfering RNA (siRNA), inhibited the invasion of U87MG promoted by IL-6 with concomitant down-regulation of MMP-2. Furthermore, rapid up-regulation of fascin-1 (a cell motility-related protein) induced by IL-6 was apparent in U87MG cells. However, this up-regulation of fascin-1 was not inhibited by JSI-124 or siRNA. These results suggest that the STAT3 pathway and fascin-1 may play crucial roles in the invasiveness of U87MG cells promoted by IL-6.

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“…Subsequently, Janus kinase (JAK) and the signal transducers and activators of transcription (STAT) are phosphorylated, which activate target genes that mediate cell growth and survival, differentiation, cell mobility and angiogenesis (19,20). The aberrant production and increased secretion of IL-6 in cancer patients is profoundly linked to tumor progression and poor prognosis in many cancer types, including lung cancer (21)(22)(23). IL-6R has been targeted for cancer treatments, resulting in cell growth inhibition or reduced angiogenesis (24,25).…”

Section: Introductionmentioning

confidence: 99%

Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells

Cho

et al. 2012

Int J Oncol

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Abstract. IL-6/6R signaling is closely associated with tumor growth and poor prognosis. Although there is evidence that interleukin-6 receptor (IL-6R)-mediated signaling promotes the growth and malignancy of cancer, the role of IL-6R in cancer stem cells (CSCs) is poorly defined. This study investigated the role of IL-6R in the proliferation of CSCs. Sphere-forming cells were isolated from the H460 non-small cell lung cancer (NSCLC) cell line and identified as CSCs using confocal microscopy, RT-PCR and WST-1 assay. The H460 spheres demonstrated the typical characteristics of CSCs, including CD133 expression, upregulation of Nanog, self-renewal, and drug resistance to methotrexate (MTX) and fluorouracil (5-FU). The release of IL-6R and its ligand, IL-6, were quantitatively determined and compared between CSCs and non-CSCs. The concentration of soluble IL-6R (sIL-6R) was remarkably high in CSCs compared to that in non-CSCs. Furthermore, significant upregulation of the IL-6R gene was also observed in the CSCs. The growth of CSCs was significantly inhibited by transfection with IL-6R small-interfering RNA (siRNA), as well as with the IL-6R monoclonal antibody (mAb). In addition, blocking both IL-6R and IL-6 using siRNA or mAbs intensified the inhibition of CSC proliferation. These findings indicate that IL-6R is present in CSCs and has an important role in the proliferation of CSCs in the H460 lung cancer cell line. Therefore, we suggest that IL-6R is both a viable target for the development of CSC-directed lung cancer therapeutics and a potential CSC marker in NSCLC.

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Interleukin-6 gene amplification and shortened survival in glioblastoma patients

Cited by 123 publications

References 11 publications

Interleukin‐6 and its receptor in cancer

Interleukin‐6 and its receptor in cancer

IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1

Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells

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