Soluble interleukin-2 receptor as a factor associated with angiogenesis in gastric cancer

Abstract

Angiogenesis serves a role in the growth, metastasis and prognosis of tumors. The aim of the present study was to evaluate the angiogenic ability and clinical significance of the immune biomarker soluble interleukin‑2 receptor (sIL‑2R) in gastric cancer (GC) patients. Serum levels of sIL‑2R were measured in 35 GC patients with different stages of disease and 32 healthy individuals, and it was investigated whether the levels were associated with angiogenesis factors, including vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)‑β1. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without recombinant human (rh)sIL‑2R, VEGF and TGF‑β1 for 24 h, and then the HUVECSs were harvested to determine the degree of angiogenesis. The supernatants were also collected for VEGF and TGF‑β1 testing. Serum levels of sIL‑2R were higher in GC patients than in healthy individuals, as were the levels of VEGF and TGF‑β1. In addition, serum levels of sIL‑2R were positively associated with the levels of VEGF and TGF‑β1. Angiogenesis of HUVECs was also increased by rhsIL‑2R pretreatment. VEGF and TGF‑β1 secretion were also incre-ased in supernatants that were pretreated with rhsIL‑2R. The results of the present study suggested that serum levels of sIL‑2R contributes to the pathophysiology of GC progression and may be used as a prognostic biomarker for GC.

Gastric carcinogenesis: a comprehensive review of the angiogenic pathways

“…The regulation of several proangiogenic factors such as VE-cadherin, MMPs-2 and 9, MT1-MMP, p-ERK, β-catenin, 23 p-FAK, or p-paxillin was reported to be controlled by an oncogenic long non-coding RNA-MALAT1-which overexpression correlates with poor clinical outcome of GC patients [133]. Angiogenesis is also regulated and stimulated by a vast number of interleukins and their receptors among which IL-1α, IL-8 (via high-mobility group box-1 (HMGB1) contribution), IL-17 (through STAT3 pathway), or soluble interleukin-2 receptor (sIL-2R) are considered to be of the highest importance regarding GC patients; except for neovascularization, IL-1α is involved in liver metastasis of GC [134][135][136][137].…”

Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies

“…Additionally, ongoing research efforts aim to identify reliable biomarkers of response to sIL-2R and IL-2Rα therapies [ 14 , 23 , 177 – 198 , 200 ]. It is anticipated that such biomarkers could help predict which patients would benefit most from these therapies [ 201 – 223 , 254 , 255 ]. The burgeoning understanding of IL-2’s molecular mechanisms and cellular influences not only enhances its therapeutic potential in treating autoimmune diseases and cancer but also sets a new paradigm in immunotherapy [ 68 , 71 , 153 , 226 – 228 ].…”