Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines

Kim, Ke; Song, Hyun Keun; Ts, Kim; Yoon, Do‐Young; Cw, Kim; Bang, Si Ra; Dy, Hur; Park, H; Dh, Cho

doi:10.1038/sj.onc.1209926

Cited by 77 publications

(65 citation statements)

References 20 publications

(21 reference statements)

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“…1A shows the expression of VEGFR-3 on SNU-601 cells. It was previously reported that VEGFR-2 is strongly expressed on SNU-601 cells (3). Exogenous VEGF-D (50 ng/ml) significantly enhanced cell migration in both a dose-and time-dependent manner (Fig.…”

Section: Il-18 Plays An Important Role In Vegf-d-enhanced Migrationmentioning

confidence: 51%

“…This indicates that the regulation of the IL-18 secretion process is critical for tumor progression. In our previous study, we reported that vascular endothelial growth factor (VEGF) 3 165 enhanced IL-18 production in human gastric cancer cells, resulting in increased IL-18-mediated migration (3). VEGF, a member of the plateletderived growth factor family, is known as the most potent proangiogenic factor.…”

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confidence: 99%

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Expression of ADAM33 Is a Novel Regulatory Mechanism in IL-18-Secreted Process in Gastric Cancer

Kim

Song

Hahm³

et al. 2009

The Journal of Immunology

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IL-18 has recently been reported to play a critical role in tumor migration, invasion, and metastasis. Because IL-18 has various biological activities after its secretion as an 18 kDa mature form, the regulation of the IL-18 secretion process is an important step in tumor progression. This study investigated the implication of IL-18 in vascular endothelial growth factor (VEGF)-D-regulated migration, along with the role of the IL-18 secretion process. VEGF-D enhanced cell migration, which was then blocked by inhibiting IL-18. VEGF-D increased IL-18 expression and secretion, suggesting that IL-18 is a critical mediator for VEGF-D-enhanced migration. VEGF-D induced a disintegrin and metalloprotease 33 (ADAM33) expression, which has a metalloproteinase domain. VEGF-D-enhanced IL-18 secretion and cell migration were inhibited by ADAM33 knock-down. Moreover, cell proliferation was considerably reduced in ADAM33 small interfering RNA transfectants. In conclusion, ADAM33 has a key role in gastric cancer pathogenesis by up-regulating IL-18 secretion process, resulting in increased cell migration and proliferation.

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Section: Il-18 Plays An Important Role In Vegf-d-enhanced Migrationmentioning

confidence: 51%

mentioning

confidence: 99%

Expression of ADAM33 Is a Novel Regulatory Mechanism in IL-18-Secreted Process in Gastric Cancer

Kim

Song

Hahm³

et al. 2009

The Journal of Immunology

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“…Inhibiting IL-18 markedly reduced the level of Vascular endothelial growth factor (VEGF)-enhanced migration, and IL-18 increases cell migration directly through filamentous-actin polymerization and tensin down regulation (Kim et al, 2007). Human IL-18 induces micro vascular endothelial cell (HMVEC) migration.…”

Section: Il-18 Enhances Angiogenesismentioning

confidence: 99%

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Kuppala¹,

Syed²,

Bandaru³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

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“…However, previous studies have shown that IL-18 also exerts favorable effects on tumor progression (2-4). mutual stimulation between this cytokine and vascular endothelial growth factor (20,21). Some studies have also suggested that IL-18 stimulates migration of tumor cells in a matrix metalloproteinase-dependent manner (22,23).…”

Section: Discussionmentioning

confidence: 98%

Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice

Jung

Kim²,

Cho

et al. 2009

Oncol Rep

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Abstract. Cytokines are a protein family of regulatory factors derived from tumors and their environmental components that contribute to the growth, invasion and metastasis of breast cancer. However, the way in which tumor progression and cytokines regulate each other is not well understood. In this study, we used an oligoDNA microarray to assess the kinetic expression profile of cytokine genes in tumor tissues and lymph nodes during the progression of tumor growth in mice that had been subcutaneously challenged with breast adenocarcinoma SB5b cells. Our results demonstrated that IL-15, IL-17, IL-18 and IL-18 binding protein (IL-18bp), which are associated with inflammation, were increased in tumor tissues. Conversely, chemokines and their receptors, including CXCR4/CXCL12, CCR7/CCL21, CCL9, CXCL9 and CCL12, were overexpressed in lymph nodes during tumor growth. Furthermore, RT-PCR and Western blot analysis revealed that IL-18, a pro-angiogenic factor in tumors, was up-regulated in tumor tissues. Interestingly, CCR3, IL-1R2, SOCS and IL-20 were up-regulated in tumor tissues, but down-regulated in lymph nodes during tumor growth. This result suggests that the expression of cytokines and cytokine-related genes was differentially regulated, which resulted in a beneficial effect for tumor progression.

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Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines

Cited by 77 publications

References 20 publications

Expression of ADAM33 Is a Novel Regulatory Mechanism in IL-18-Secreted Process in Gastric Cancer

Expression of ADAM33 Is a Novel Regulatory Mechanism in IL-18-Secreted Process in Gastric Cancer

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice

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