Clinical significance of serum interleukin-18 (IL-18) levels in patients with gastric cancer

Taş, Faruk; Yasasever, Ceren Tilgen; Karabulut, Senem; Taştekin, Didem; Duranyıldız, Derya

doi:10.1016/j.biopha.2014.12.040

Cited by 27 publications

(23 citation statements)

References 7 publications

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“…Notably, the level of IL-1β and IL-18 were found to be significantly elevated in various types of malignancies. These cytokines can facilitate pro-carcinogenic activity by triggering the secretion of VEGF, FGF2 and STAT3, and subsequently support cancer survival and distant metastasis [23-25]. Therefore, elucidating the molecular network of inflammasomes has become a novel strategy for cancer prevention research.…”

Section: Introductionmentioning

confidence: 99%

The inflammasome: an emerging therapeutic oncotarget for cancer prevention

Wang

et al. 2016

Oncotarget

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Deregulated inflammation is considered to be one of the hallmarks of cancer initiation and development regulation. Emerging evidence indicates that the inflammasome plays a central role in regulating immune cells and cytokines related to cancer. The inflammasome is a multimeric complex consisting of NOD-like receptors (NLRs) and responds to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli. Several lines of evidence suggests that in cancer the inflammasome is positively associated with characteristics such as elevated levels of IL-1β and IL-18, activation of NF-κB signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process. A number of NLRs, such as NLRP3 and NLRC4 are also highlighted in carcinogenesis and closely correlate to chemoresponse and prognosis. Although conflicting evidence suggested the duplex role of inflammasome in cancer development, the phenomenon might be attributed to NLRs difference, cell and tissue type, cancer stage, and specific experimental conditions. Given the promising role of inflammasome in mediating cancer development, precise elucidation of its signaling network and pathological significance may lead to novel therapeutic options for malignancy therapy and prevention.

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Section: Introductionmentioning

confidence: 99%

The inflammasome: an emerging therapeutic oncotarget for cancer prevention

Wang

et al. 2016

Oncotarget

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“…In our previous studies, we demonstrated that IL-18 had a tumor suppressive function in oral squamous cell carcinoma cells [9,11,12]. However, other studies showed that IL-18 was able to promote tumor development and progression by showing higher levels of serum IL-18 in patients with gastric cancer [13] or oral cancer [14]. Jurecekova et al [15] assessed the level of IL-18 in prostatic cancer and discovered that IL-18 expression was associated with advanced grades of tumor and inversely with tumor prognosis and invasion.…”

mentioning

confidence: 97%

Interleukin‐18 expression in oral squamous cell carcinoma: its role in tumor cell migration and invasion, and growth of tumor cell xenografts

et al. 2018

FEBS Open Bio

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Oral squamous cell carcinoma ( OSCC ) is one of the most common head and neck malignancies. Advanced stages of the disease are associated with poor survival, highlighting a need for new treatment modalities. We previously showed that the proinflammatory cytokine interleukin‐18 ( IL ‐18) has a tumor suppressive role in OSCC . Here, we investigated the effects of IL ‐18 on proliferation, migration, and invasion of OSCC cells ex vivo and in vitro , and in nude mouse xenografts. We report that expression of tankyrase 2 ( TNKS 2), β‐catenin, and N‐cadherin was higher in tumor cells than in normal mucosae, whereas the expression of IL ‐18 and E‐cadherin was higher in normal than in tumor tissues. Elevated expression of IL ‐18 ( P < 0.01) and E‐cadherin ( P = 0.034) was associated with tumor differentiation, whereas expression of TNKS 2 ( P < 0.01), β‐catenin ( P = 0.012), and N‐cadherin ( P < 0.01) was associated with tumor de‐differentiation. Furthermore, compared with the vector control, IL ‐18 overexpression promoted tumor cell migration and invasion ( P < 0.01), but inhibited growth of tumor cell xenografts ( P < 0.05). At the protein level, expression levels of IL ‐18 ( P < 0.01), TNKS 2 ( P = 0.045), β‐catenin ( P = 0.028), and N‐cadherin ( P = 0.068) were upregulated in tumor cells after IL ‐18 overexpression compared with those of the vector control mice, whereas expression levels of E‐cadherin ( P = 0.045) were decreased. In conclusion, our data suggest that IL ‐18 overexpression induces oral SCC cell invasion and metastasis by promoting the tumor cell epithelial–mesenchymal transition via the Wnt/β‐catenin signaling pathway.

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“…Recent reports have also revealed relationships between several ILs and nasopharyngeal, prostate, cervical, pancreatic, gastric, breast, and esophageal cancers, in addition to NHL (Guney et al, 2009;Chen et al, 2015;Li et al, 2015;Sun et al, 2015;Tas et al, 2015;Yu et al, 2015;Karabulut et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to multiple activities relating to its immunity-stimulating capacity, it exerts antitumor effects mediated by enhancement of NK cell activity, reduction of tumorigenesis, induction of apoptosis, and inhibition of angiogenesis in tumor cells. Recent data suggest that abnormal IL-18 production contributes to the pathogenesis of malignancies and may influence clinical outcome (Tas et al, 2015). Increased IL-18 levels have been detected in hematologic malignancies, for which this cytokine may serve as a sensitive serum marker of therapeutic effect and clinical course (Taniguchi et al, 1997;Takubo et al, 2000b).…”

Section: Discussionmentioning

confidence: 99%

“…IL-18, a member of the IL-1 family, is synthesized as an inactive precursor before being converted to a bioactive form because of cleavage by an IL-1b-converting enzyme (Tas et al, 2015). IL-18 is a 18.3-kDa multifunctional cytokine synthesized by Kupffer cells, activated macrophages, keratinocytes, intestinal epithelial cells, osteoblasts, and adrenal cortex cells (Gillespie and Horwood, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of interleukin-4 and interleukin-18 levels in aggressive non-Hodgkin’s lymphoma patients

et al. 2016

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ABSTRACT. Strong evidence indicates that tumor growth can be actively controlled by the immune system, and interleukins (ILs) are known to play an influential role in immune response regulation. Moreover, inflammatory cytokines are significantly involved in lymphoma pathogenesis. We aimed to investigate serum levels of IL-4 and IL-18 in aggressive non-Hodgkin's lymphoma (A-NHL) patients and their relationship with prognostic parameters and therapy outcome. These serum factors were measured by enzyme-linked immunosorbent assay in 46 patients with pathologically verified A-NHL before and after chemotherapy, and in 20 healthy controls. No significant difference in serum IL-4 (P = 0.11) and IL-18 (P = 0.261) levels was observed between the A-NHL and controls groups. None of the prognostic parameters analyzed significantly correlated with serum IL-4 concentration, while only lactate dehydrogenase (LDH) measurements were associated with IL-18 values. Serum IL-18 was elevated in the patients with high LDH levels compared to those exhibiting normal values (P = 0.045). In addition, no correlation was found between the concentrations of serum IL-4 and IL-18 in A-NHL patients (r = 0.188, P = 0.187). While IL-18 values did not change, serum IL-4 levels decreased following chemotherapy, independently from treatment response (P = 0.002). Our study is the first to report the response of serum IL-4 levels to chemotherapy. In conclusion, although IL-4 serum concentration has no diagnostic role, it is sensitivite to standard chemotherapy in A-NHL. However, serum IL-18 measurements have no diagnostic or prognostic role in this disease.

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Clinical significance of serum interleukin-18 (IL-18) levels in patients with gastric cancer

Cited by 27 publications

References 7 publications

The inflammasome: an emerging therapeutic oncotarget for cancer prevention

The inflammasome: an emerging therapeutic oncotarget for cancer prevention

Interleukin‐18 expression in oral squamous cell carcinoma: its role in tumor cell migration and invasion, and growth of tumor cell xenografts

Clinical significance of interleukin-4 and interleukin-18 levels in aggressive non-Hodgkin’s lymphoma patients

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