Overexpression of SPARC gene in human gastric carcinoma and its clinic–pathologic significance

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: High Expression Of Il-32 In Gastric Cancer Is Correlated Witmentioning

confidence: 86%

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

Wang

Clinical Cancer Research

et al. 2014

102

“…Clinical data suggest a correlation between tumoral SPARC expression and the positive clinical outcome of patients treated with Nab-PTX (24,25). Indeed, SPARC expression has been confirmed in both gastric cancer tissues and the microenvironment of peritoneal metastasis (33)(34)(35). Accordingly, it has been hypothesized that Nab-PTX may take advantage of each of these mechanisms to reach the microenvironment of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer

et al. 2014

“…Previously, studies on the mechanisms and roles of C-X-C motif chemokine receptor type 2 (CXCR2) in GC were performed (8,9). CXCR2 belongs to the chemokine receptor family, which consists of G-protein-coupled receptors containing 7 transmembrane domains (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

Yang

Han

et al. 2016

Oncology Letters

Abstract. C-X-C motif chemokine receptor type 2 (CXCR2), a key regulatory protein, has been associated with multiple roles in the progression of numerous tumors, including gastric adenocarcinoma (GA). However, the mechanism of CXCR2 in the development of tumors remains controversial and unclear. In a previous study, the expression of CXCR2 and interleukin-22 receptor 2 (IL-22BP) was observed in GA. This promoted the present study, which aimed to explore the association between the two proteins, and to further analyze their roles in GA. CXCR2 and IL-22BP protein expression was analyzed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in gastric cancer (GC) tissue, additionally confirmed via western blotting and immunocytochemical analysis in the MKN-45, BGC-823 and SGC-7901 cell lines. The association between expression levels and clinicopathological characteristics was evaluated by the Mann-Whitney U and Kruskal-Wallis tests. Using Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with non-cancerous tissue, CXCR2 and IL-22BP were over expressed (P<0.001 and P<0.001, respectively), and were observed mainly in the cytoplasm (P=0.022 and P=0.014, respectively) in GA. The associated protein and messenger RNA levels were analyzed, and coexpression was identified. Increased expression and more positive cases of CXCR2 and IL-22BP were observed with advanced pathological tumor-node-metastasis (p-TNM) stage in GC (P<0.001 and P<0.001, respectively), as well as the presence and absence of lymph node metastasis (LNM) (P=0.003 and P=0.041, respectively) and deep or superficial muscular invasion (P=0.002 and P=0.004, respectively). In addition, an association between IL-22BP and tumor diameter was indicated (P=0.021). In a Kaplan-Meier analysis, compared with negative expression, the two proteins identified a group of patients with the shortest OS. Cox proportional hazard models revealed that the two proteins, in addition to p-TNM stage, LNM and depth of invasion, predicted a short time to OS. The coexpression of CXCR2 and IL-22BP was demonstrated in GA, which may indicate that CXCR2 is involved in more complex mechanisms and roles, and indicate a poor outcome in GA progression.