IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: Evidence for a role as an autocrine growth factor

Nicholl, Michael B.; Ledgewood, Chelsea L.; Chen, Xuhui; Bai, Qian; Qin, Chenglu; Cook, Kathryn M.; Herrick, Elizabeth; Diaz-Arias, Alberto A.; Moore, Bradley J.; Fang, Yujiang

doi:10.1016/j.cyto.2014.06.020

Cited by 68 publications

(68 citation statements)

References 38 publications

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“…In addition to the EBI3 expression level, increased expression levels of IL-12p35 and IL-27p28 were also been found in the breast cancer tissues compared with the normal controls. Furthermore, EBI3 was noted to be positively correlated with IL-12p35 expression, indicating that IL-35 might be involved in the progression of breast cancer, which is in accordance with the results found in pancreatic cancer and colorectal carcinoma, which also demonstrated the crucial role of IL-35 during tumor progression [17,19].…”

Section: Correlation Between Ebi3 Expression and Overall Survival Of supporting

confidence: 79%

Upregulated EBI3 Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Jiang

Liu

2018

Oncol Res Treat

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Background and Aim: So far, the understanding of the role of Epstein-Barr virus-induced gene 3 (EBI3) in breast cancer has been limited. This study uncovers the functional role and clinical significance of EBI3 in breast cancer patients. Patients and Methods: The expression levels of EBI3, IL-27p28, and IL-12p35 were measured by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Correlations of EBI3 expression with IL-27p28 and IL-12p35 expression were analyzed using Pearson's correlation assay. The prognostic performance of EBI3 was assessed via Kaplan-Meier survival assay and Cox regression analysis. Results:EBI3 expression was increased in cancerous tissues compared with the controls (P < 0.05). This overexpression of EBI3 was correlated with lymph node metastasis and clinical stage (both P < 0.05). Besides, elevated expression of EBI3 was usually found in patients with positive lymph node metastasis (P < 0.05), and similar results were obtained in advanced clinical-stage breast cancer cases (P < 0.05). Increases in both IL-27p28 and IL-12p35 expression were identified in breast cancer tissues (all P < 0.05), and IL-12p35 expression was found to be associated with EBI3 expression (R = 0.888, P < 0.001). Survival curves revealed that high EBI3 expression was correlated with poor overall survival (log-rank P < 0.05). The Cox analysis indicated that EBI3 was an independent prognostic factor in breast cancer. Conclusion: Taken together, overexpression of EBI3 was associated with poor prognosis and might be involved in the progression of breast cancer.

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Section: Correlation Between Ebi3 Expression and Overall Survival Of supporting

confidence: 79%

Upregulated EBI3 Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Jiang

Liu

2018

Oncol Res Treat

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“…Interleukin-35 (IL-35) is a newly discovered member of the interleukin family with anti-inflammatory and immune inhibitory effects [7,8]. Recently, it has been demonstrated that IL-35 plays an important role in tumor progression, including lung cancer [9], pancreatic cancer [10], nasopharyngeal carcinoma [11], gastric cancer [12], hepatocellular carcinoma [13][14][15], breast cancer [16,17], renal cell carcinoma [18] and colorectal cancer [19,20]. However, the underlying mechanisms of IL-35 in NSCLC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression

Sun¹,

Zheng²,

Meng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Lung cancer continues to be the leading cause of cancer related deaths worldwide due to its high incidence, malignant behavior and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. Methods: We first evaluated the IL-35 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by realtime PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs were assessed. Results: IL-35 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The down-regulation of IL-35 was significantly correlated with the results of American Joint Committee on Cancer stage, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-35 in NSCLC cells suppressed cell migration, invasion, proliferation, colony formation through suppressing β-catenin. IL-35 inhibited NSCLC formation in the mice model and sensitize the cancer cells to chemotherapy drugs. Conclusion: Our results showed that IL-35 plays an inhibitory role in NSCLC development and function as a novel prognostic indicator and a potential therapeutic target.

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“…In addition, the authors identified that IL-35 upregulates gp130 to mediate cancer cell resistance to CTL destruction (15). Nicholl et al (20) stated that IL-35, an autocrine growth factor for pancreatic adenocarcinoma, promotes proliferation and inhibits apoptosis. In a study by Fan et al (22) IL-35 was considered to be associated with the genesis of gastric cancer.…”

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

confidence: 99%

“…However, distinct from other members of the IL-12 family, IL-35 is a novel inhibitory cytokine and suppresses T cell proliferation through the unconventional signal transducer and activator of transcription (STAT) 1-STAT4 heterodimer signaling pathway (18). Previous studies have focused on the involvement of IL-35 in tumor immunity, and revealed that IL-35 is involved in tumor development and progression and is associated with poor prognosis (14,15,(20)(21)(22).…”

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

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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IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: Evidence for a role as an autocrine growth factor

Cited by 68 publications

References 38 publications

Upregulated <b><i>EBI3</i></b> Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Upregulated <b><i>EBI3</i></b> Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression

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

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