The role of circulating IL‐8 and VEGF protein in the progression of gastric cancer

Abstract

Both vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) play an important role in the progression of gastric cancer (GC). In this study, we investigated whether circulating levels of VEGF or IL-8 in drainage veins of GC patients were correlated with any clinicopathological factors. Thirty-seven patients with primary GC who underwent gastrectomy at our department between 1999 and 2002 were analyzed. Blood samples were drawn from a peripheral vein just before surgery and from a drainage vein immediately after laparotomy. Plasma VEGF levels were significantly higher than those in 10 healthy controls. There was no correlation between VEGF levels in drainage veins and any clinicopathological variable, whereas there was a significant relationship in the case of VEGF levels in peripheral veins; the levels were higher in patients with venous invasion. We found a significant relationship between IL-8 levels in drainage veins and both tumor size and lymph node metastasis, whereas no significant relationship between IL-8 levels in peripheral veins and any variable was found. There was no correlation between VEGF and IL-8 levels in drainage veins. Large tumors, deeply invasive tumors, lymph node involvement, venous invasion and high IL-8 levels in drainage veins were all significantly associated with shorter diseasefree survival, although multivariate analysis revealed that lymph node involvement was the only independent prognostic factor. In conclusion, the measurement of IL-8 levels in drainage veins of GC patients may reflect production mainly by the primary lesion and is valuable as an indicator of risk for recurrent disease.

Evaluation of Serum Interleukin-8 (CXCL8) Concentrations in Tumor Bearing Dogs

“…In this study a significant correlation between augmented serum CXCL8 concentrations and an increasing tumor size was found, being consistent with previous studies (Konno et al, 2003;Ren et al, 2003;Ahmed et al, 2006). Locally, CXCL8 is known to moderate tumor growth and survival through neovascularization, as well as autocrine and paracrine mechanisms, but the exact mechanism for its raise in peripheral blood is unknown (Yuan et al, 2005;De Larco et al, 2004;Raman et al, 2007;Balkwill, 2003).…”

“…Additionally, serum CXCL8 is susceptible to changes in its concentration due to dilution and its reliability to predict local changes should therefore be questioned. Although some studies showed a congruent increase in local and systemic CXCL8 values (De Andrés et al, 2013;Tamura et al, 2013) a study by Konno et al (2003) found a relationship between CXCL8 and a variety of tumor parameters in drainage veins of gastric cancer, whereas no significant relationship in peripheral veins (Konno et al, 2003). Moreover, the producing cells as well as the function of local and systemic CXCL8 may differ so that both should be included and compared in future studies.…”

“…Although the major production of CXCL8 occurs locally as an adaptive response of cancer cells to withstand environmental or chemical stresses (Kim et al, 2014;Raman et al, 2007;Desbaillets et al, 1997;Shi et al, 2001), its concentration has been found to be also elevated in the blood of human and canine cancer patients (Yokoe et al, 1996;Ueda et al, 1994;Veltri et al, 1999;Gelaleti et al, 2012;De Andrés et al, 2013;Konno et al, 2003;Ugurel et al, 2001;Ren et al, 2003;Benoy et al, 2004;Lokshin et al, 2006). On the one hand, cells within the tumor tissue are known to secrete CXCL8 that may partly escape the tumor environment and reach the bloodstream through the vast amount of blood vessels that usually nourish a tumor.…”

VEGF significance in peritoneal recurrence from gastric cancer

“…Therefore, we speculate that treatment with VEGF antibody might prevent peritoneal recurrence of gastric cancer. Konno et al [23] reported that, in gastric cancer patients, VEGF levels in the peripheral veins were higher in patients with venous invasion. In our study, the mean number of tumor vessels patients with in type 3 or type 4 was significantly higher than that in patients with type 2, and the mean number of tumor vessels in those with high expression of VEGF tended to be greater than that in those with low VEGF expression.…”

MiR-129-5p is down-regulated and involved in migration and invasion of gastric cancer cells by targeting interleukin-8

“…Moreover, IL-8 is considered as a target for therapeutic intervention of cancers [26]. Increased serum levels of circulating IL-8 has been reported in GC patients than healthy controls [27,28], and IL-8 has been suggested to be associated with adhesion, migration, invasion and chemosensitivity, vascularity of GC [29][30][31]. In addition, previous studies have shown that several miRNAs, such as miR-520b, miR-106a, miR-106b, miR-23a, and miR-93 [32][33][34][35], are identified in diverse diseases by targeting IL-8 gene expression.…”