IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells

Long, Jun; Zhang, Xulong; Wen, Mingjie; Kong, Qingtao; Lv, Zhe; An, Yongbo; Wei, Xiao-Qing

doi:10.1016/j.bbrc.2012.11.004

Cited by 56 publications

(72 citation statements)

References 22 publications

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“…Previously, a series of findings revealed that IL-35 is a vital component in the development and progression of cancers, including colorectal and pancreatic cancer (11,22). As a secretory glycoprotein, EBI3 dimerizes with p35-associated subunits to form IL-35 cytokines (23).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of Epstein-Barr virus-induced gene 3 in cervical cancer: Association with clinicopathological parameters and prognosis

Hou¹,

Dong²,

Liu³

et al. 2015

Oncology Letters

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Abstract. Epstein-Barr virus-induced gene 3 (EBI3) encodes a secretory glycoprotein, and has previously been identified as upregulated in a series of cancers. However, the clinical significance of EBI3 in cervical cancer and the potential of EBI3 as a therapeutic target for this disease have not been elucidated. In the present study, EBI3 expression was analyzed by immunohistochemistry in 90 clinicopathologically characterized cervical cancer tissue samples. The association between EBI3 expression and survival of patients with cervical cancer was also analyzed. The expression level of EBI3 in cervical cancer tissues was found to be significantly increased compared with the expression levels in the normal squamous epithelium. In addition, EBI3 expression was significantly correlated with the clinical stage and size of tumors (P<0.05). Furthermore, the presence of EBI3 expression was associated with a poor prognosis compared with patients without EBI3 expression. Multivariate analysis revealed that EBI3 expression was an independent predictor of overall survival (hazard ratio, 4.032; 95% confidence interval, 1.538-7.436; P=0.035). To the best of our knowledge, the present results indicate for the first time that EBI3 expression is significantly associated with the progression and poor prognosis of cervical cancer. EBI3 may be a potential prognostic marker and a therapeutic target in cervical cancer.

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Section: Discussionmentioning

confidence: 99%

“…proliferation of lung cancer cells (22). However, the precise function of EBI3 is not well understood in cervical cancer.…”

Section: A B C D E Fmentioning

confidence: 99%

Expression of Epstein-Barr virus-induced gene 3 in cervical cancer: Association with clinicopathological parameters and prognosis

Hou¹,

Dong²,

Liu³

et al. 2015

Oncology Letters

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“…However, there are still contradictory results. Long et al (13) demonstrated that over-expression of IL-35 in human cancer cells inhibits cancer cell growth in vitro, and that IL-35 suppresses tumor growth via cell cycle arrest at the G1 phase and substantially sensitized cells to serum starvation-induced apoptosis through downregulation of cyclin D1 and survivin expression.…”

Section: The Association Between Il-35 Expression and The Prognosis Omentioning

confidence: 99%

“…However, the precise underlying mechanism behind the involvement of IL-35 in malignant diseases has yet to be elucidated. Previous studies have revealed that IL-35 is expressed in several tumor tissues, including lung and colon cancer, esophageal, hepatocellular and cervical carcinoma (13,14). IL-35 has been demonstrated to promote tumor angiogenesis and inhibit an antitumor cytotoxic lymphocyte (CTL) response (15).…”

Section: Introductionmentioning

confidence: 99%

IL-35 expression is increased in laryngeal squamous cell carcinoma and in the peripheral blood of patients

Jiang

et al. 2017

Oncology Letters

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Abstract. has been proposed as a novel immune-suppressing cytokine. However, the function of IL-35 in malignant diseases is yet to be elucidated. The present study investigated IL-35 expression levels in laryngeal squamous cell carcinoma (LSCC) tissues and the peripheral blood of patients to explore the potential involvement of IL-35 in LSCC progression. In the present study, IL-35 expression levels in tissues and peripheral blood were analyzed by reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The association between IL-35 expression levels and clinical characteristics was also evaluated. The present results demonstrated that IL-35 expression in tumor tissues was significantly higher than in adjacent normal tissues, and a significant association between IL-35 expression levels in tissues and the tumor site was detected. Furthermore, the expression of IL-35 in the peripheral blood of patients was significantly decreased subsequent to tumor resection. No correlation between peripheral blood IL-35 expression and clinical characteristics was detected. In conclusion, the present study demonstrated that IL-35 is highly expressed in LSCC tissues and in the peripheral blood of patients with LSCC. There was a notable, significant reduction of peripheral blood IL-35 expression following surgical resection of tumors. These results may be useful for diagnostic or therapeutic purposes in patients with LSCC.

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“…In another study, Long et al showed that IL-35 has antitumor potential, as its overexpression in various human cancer cell lines resulted in cell growth inhibition in vitro. IL-35 overexpression induces G1 cell cycle arrest and increases apoptosis via TNF-α and IFN-γ stimulation and downregulation of cyclin D1, survivin, and Bcl 2 expression (Long et al, 2013 (Li et al, 2011). CD4 + Th17 cells secreting 1L-17 have also been implicated to have a role in solid tumors.…”

Section: Cd28mentioning

confidence: 99%

Failure of immunological cells to eradicate tumor and cancer cells: an overview

Sharma¹,

Talukdar²,

Malik³

et al. 2014

Turk J Biol

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Inflammation can be broadly understood as a successive immune response of an organism's immune system towards nonnative or foreign antigens. This is a protective mechanism of the immune system, mediated by diverse immunological cells, to ensure homeostasis of an individual. Once activated, these immunological cells release a number of cytokines, chemokines, reactive oxygen species, reactive nitrogen species, histamines, prostaglandins, and other materials leading to inflammation. Tumor cells express altered proteins due to mutations of their genes, DNA modifications such as histone modification, DNA methylation, or other mechanisms of altered protein expression. The body's immunological cells actively recognize these altered proteins, now acting as tumor antigens, and eliminate the tumor cell; this is popularly known as tumor immunosurveillance. However, in unmanaged or inexorable circumstances, tumor cells escape from immunosurveillance mechanisms. This ultimately leads to the cascading events of cancer development and progression. T regulatory cells, tumor-associated macrophages, and myeloid-derived suppressor cells are pronounced cells involved in immunosuppression. These cells not only dodge the immune system's surveillance but also significantly increase the survival, proliferation, and metastasis rates of tumor cells. They hinder T cytotoxic activation by secreting inhibitory cytokines (which inhibit the antitumor activity of natural killer cells) along with dendritic cells and disrupt presentation of antigens, ultimately leading to cancer development. On their own, these cells have emerged as promising therapeutic targets in cancer immunotherapy. This review highlights some of the mechanisms by which these cells escape immunosurveillance and mediate immune suppression.

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IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells

Cited by 56 publications

References 22 publications

Expression of Epstein-Barr virus-induced gene 3 in cervical cancer: Association with clinicopathological parameters and prognosis

Expression of Epstein-Barr virus-induced gene 3 in cervical cancer: Association with clinicopathological parameters and prognosis

IL-35 expression is increased in laryngeal squamous cell carcinoma and in the peripheral blood of patients

Failure of immunological cells to eradicate tumor and cancer cells: an overview

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