Interleukin-6 directly influences proliferation and invasion potential of head and neck cancer cells

Kanazawa, Takemichi; Nishino, Hiroshi; Hasegawa, Masahiro; Ohta, Yasushi; Iino, Yukiko; Ichimura, Keiichi; Noda, Yutaka

doi:10.1007/s00405-007-0264-6

Cited by 46 publications

(57 citation statements)

References 28 publications

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“…Interleukin-6 directly influences proliferation and invasion potential of head and neck cancer cells. These results suggest a direct influence of IL-6 on cell proliferation and its invasion potential as the first step of tumor metastasis (31). Expression of the MAPK extracellular signal-regulated kinase (ERK1/2) is associated with NF-κB-A Figure 5.…”

Section: Discussionmentioning

confidence: 92%

Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation

Riebe¹,

Pries²,

Kemkers³

et al. 2007

Int J Mol Med

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Abstract. Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently diagnosed cancers. It is believed that tumor production of various immune suppressive mediators contributes to massively impaired immune functions, but the underlying signal transduction pathways are mostly unknown. Phosphorylation levels of MAP (mitogen-activated protein) kinase p38 were analyzed in permanent cell lines as well as in solid tumor tissue of HNSCC using flow cytometry and SDS-PAGE. Cytokine secretion was determined using the Cytometric Bead Array Flex Set system. MAP kinase p38 was shown to be activated in HNSCC by phorbol 12-myristate 13-acetate. Activation of p38 led to decreased cell proliferation and increased secretion of cytokines IL-6 and IL-8 in HNSCC. Our data provide novel insights into the origin of the HNSCC microenvironment. A better understanding of these molecular mechanisms in HNSCC is essential for novel drug development and improvement of the clinical perspective of this tumor type.

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Section: Discussionmentioning

confidence: 92%

Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation

Riebe¹,

Pries²,

Kemkers³

et al. 2007

Int J Mol Med

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“…It has been suggested that IL-6 is involved in the host inflammatory reactions associated with cancer growth (39,40). There is suggestive evidence that IL-6 could play a role in tumorigenesis, but a clear understanding of the mechanisms of action is currently lacking (43). Beyond its circulating levels, there is presently an enormous scientific interest in the genes, receptors, and biological pathways involved with IL-6 (44).…”

Section: Discussionmentioning

confidence: 99%

Serum Prognostic Markers in Head and Neck Cancer

Meyer

Samson

Douville

et al. 2010

Clinical Cancer Research

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Purpose: Recognized prognostic factors do not adequately predict outcomes of head and neck cancer (HNC) patients after their initial treatment. We identified from the literature nine potential serum prognostic markers and assessed whether they improve outcome prediction.Experimental Design: A pretreatment serum sample was obtained from 527 of the 540 HNC patients who participated in a randomized controlled trial. During follow-up, 115 had a HNC recurrence, 110 had a second primary cancer (SPC), and 216 died. We measured nine potential serum prognostic markers: prolactin, soluble interleukin-2 (IL-2) receptor-α, vascular endothelial growth factor, IL-6, squamous cell carcinoma antigen, free β-human choriogonadotropin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and soluble epidermal growth factor receptor. Cox regression was used to identify a reference predictive model for (a) HNC recurrence, (b) SPC incidence, and (c) overall mortality. Each serum marker was added in turn to these reference models to determine by the likelihood ratio test whether it significantly improved outcome prediction. We controlled for the false discovery rate that results from multiple testing.Results: IL-6 was the only serum marker that significantly improved outcome prediction. Higher levels of IL-6 were associated with a higher SPC incidence. The hazard ratio comparing the uppermost quartile to the lowest quartile of IL-6 was 2.68 (95% confidence interval,

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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).…”

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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Interleukin-6 directly influences proliferation and invasion potential of head and neck cancer cells

Cited by 46 publications

References 28 publications

Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation

Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation

Serum Prognostic Markers in Head and Neck Cancer

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

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