Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer

Wang

Clinical Cancer Research

et al. 2014

102

Purpose: The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32-mediated migration and invasion.Experimental Design: Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo.Results: IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3b/active b-catenin as well as hypoxiainducible factor 1a (HIF-1a) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns.Conclusions: IL-32 contributes to gastric cancer progression by increasing the metastatic potential resulting from AKT, b-catenin, and HIF-1a activation. Our results clearly suggest that IL-32 is an important mediator for gastric cancer metastasis and independent prognostic predictor of gastric cancer. Clin Cancer Res; 20(9); 2276-88. Ó2014 AACR.

Section: Introductionmentioning

confidence: 99%

Interleukin-32 Increases Human Gastric Cancer Cell Invasion Associated with Tumor Progression and Metastasis

Wang

Clinical Cancer Research

et al. 2014

102

Serbian Journal of Experimental and Clinical Research

“…Higher levels of IL-32 were reported in many other cancers: melanoma, thyroid, renal cell (18,71,75). Recent studies have revealed higher expression of IL-32 in human pancreas, liver, and esophagus cancer tissues, compared with normal tissue or serum (76)(77)(78). One of the hallmarks of tumor is angiogenesis.…”

Section: Role In Cancer Biologymentioning

confidence: 99%

Interleukin-32 in Infection, Inflammation and Cancer Biology

Pavlovic

Jovanović

Arsenijević

2020

“…It is now well established that STAT3 signaling is a major intrinsic pathway driving apoptosis, inflammation, cellular transformation, survival, proliferation, invasion, angiogenesis and metastasis of cancer [10][11]. However, compelling evidence has now shown that STAT3 is constitutively activated in many human cancers [12].…”

mentioning

confidence: 99%

Critical role of IL-23 signaling in prostatic cancer

Alhasani¹,

Yousif²

2013

AJBM

Although the role of Th17 in tumor progression remains controversial, the role of IL-23 in tumor incidence and metastasis was established in the mouse model. For example, mice lacking IL-23p19 were resistant to DMBA/TPA-induced skin papilloma [6][7]. Recently, IL-23 was also reported to promote carcinogenesis and metastasis in the 3′-methylcholanthrene induced fibrosarcoma through suppressing the innate immune response [8]. However, the role of IL-23 in metastatic prostate cancer is unclear. In this study, we found that IL-23 was highly expressed in metastatic prostate cancer cells. We further proved that IL-23 could directly promote prostate cancer metastasis via a STAT3/ROR gamma signal, so we further explored the relationship between IL-23 and STAT3/ROR gamma in prostate metastasis. We found that IL-23 and STAT3/ROR gamma were highly correlated in metastatic prostate cancer cell lines directed.