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

Yan,Wen‑Feng; Nie,Chang‑Fu; Wu,Gang; Zhang,Jian‑Cheng; Zhu,Yuan‑Zeng; Zhang,Wei; Sun,Pei‑Chun

doi:10.3892/mmr.2017.7434

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

Authors:
- Wen‑Feng Yan
- Chang‑Fu Nie
- Gang Wu
- Jian‑Cheng Zhang
- Yuan‑Zeng Zhu
- Wei Zhang
- Pei‑Chun Sun
View Affiliations

Affiliations: Department of General Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China, Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Zhengzhou University, Division of Hepatobiliary and Pancreatic Surgery, Henan Tumor Hospital, Zhengzhou, Henan 450008, P.R. China
Published online on: September 7, 2017 https://doi.org/10.3892/mmr.2017.7434
Pages: 6916-6919

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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 increased 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.

View Figures

View References

1	Baniak N, Senger JL, Ahmed S, Kanthan SC and Kanthan R: Gastric biomarkers: A global review. World J Surg Oncol. 14:2122016. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Kim HS, Lee H, Jeung HC, Noh SH, Chung HC, Roh JK, Nam CM and Rha SY: Advanced detection of recent changing trends in gastric cancer survival: Up-to-date comparison by period analysis. Jpn J Clin Oncol. 41:1344–1350. 2011. View Article : Google Scholar : PubMed/NCBI
4	Ohtsu A: Chemotherapy for metastatic gastric cancer: Past, present, and future. J Gastroenterol. 43:256–264. 2008. View Article : Google Scholar : PubMed/NCBI
5	Nagini S: Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 4:156–169. 2012. View Article : Google Scholar : PubMed/NCBI
6	Wang L, Zhou R, Zhao Y, Dong S, Zhang J, Luo Y, Huang N, Shi M, Bin J, Liao Y and Liao W: MACC-1 promotes endothelium-dependent angiogenesis in gastric cancer by activating TWIST1/VEGF-A signal pathway. PLoS One. 11:e01571372016. View Article : Google Scholar : PubMed/NCBI
7	Katoh M: FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). Int J Mol Med. 38:3–15. 2016. View Article : Google Scholar : PubMed/NCBI
8	Kerbel RS: Tumor angiogenesis. N Engl J Med. 358:2039–2049. 2008. View Article : Google Scholar : PubMed/NCBI
9	Liang X, Xu F, Li X, Ma C, Zhang Y and Xu W: VEGF signal system: The application of antiangiogenesis. Curr Med Chem. 21:894–910. 2014. View Article : Google Scholar : PubMed/NCBI
10	Li T, Liu X, Shen Q, Yang W, Huo Z, Liu Q, Jiao H and Chen J: Salinomycin exerts anti-angiogenic and anti-tumorigenic activities by inhibiting vascular endothelial growth factor receptor 2-mediated angiogenesis. Oncotarget. 7:26580–26592. 2016. View Article : Google Scholar : PubMed/NCBI
11	Ma H, Gao L, Li S, Qin J, Chen L, Liu X, Xu P, Wang F, Xiao H and Zhou S: CCR7 enhances TGF-β1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer. Oncotarget. 6:24348–24360. 2015. View Article : Google Scholar : PubMed/NCBI
12	Kanazawa S, Yamaguchi K, Kinoshita Y, Komiyama Y, Muramatsu M and Nomura S: Elevation of soluble interleukin-2 receptor in patients with non-small cell lung cancer treated with gefitinib. J Cancer Res Clin Oncol. 132:719–725. 2006. View Article : Google Scholar : PubMed/NCBI
13	Iwamuro M, Shinagawa K, Okada H, Takata K, Yoshino T and Yamamoto K: Elevated soluble IL-2 receptor levels correlate with tumor bulk of follicular lymphomas with intestinal involvement. Clin Biochem. 47:191–195. 2014. View Article : Google Scholar : PubMed/NCBI
14	Eller T, Aluoja A, Maron E and Vasar V: Soluble interleukin-2 receptor and tumor necrosis factor levels in depressed patients in Estonia. Medicina (Kaunas). 45:971–977. 2009.PubMed/NCBI
15	Ni M, Yang ZW, Li DJ, Li Q, Zhang SH, Su DF, Xie HH and Shen FM: A potential role of alpha-7 nicotinic acetylcholine receptor in cardiac angiogenesis in a pressure-overload rat model. J Pharmacol Sci. 114:311–319. 2010. View Article : Google Scholar : PubMed/NCBI
16	Liu N, Zhou N, Chai N, Liu X, Jiang H, Wu Q and Li Q: Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer. BMC Cancer. 16:3212016. View Article : Google Scholar : PubMed/NCBI
17	Wang W, Wang H, Ni Y, Yao Z, Ye L and Tian J: DCT015, a new sorafenib derivate, inhibits tumor growth and angiogenesis in gastric cancer models. Tumour Biol. 37:9221–9232. 2016. View Article : Google Scholar : PubMed/NCBI
18	Rubin LA, Galli F, Greene WC, Nelson DL and Jay G: The molecular basis for the generation of the human soluble interleukin 2 receptor. Cytokine. 2:330–336. 1990. View Article : Google Scholar : PubMed/NCBI
19	Vuoristo MS, Laine S, Huhtala H, Parvinen LM, Hahka-Kemppinen M, Korpela M, Kumpulainen E and Kellokumpu-Lehtinen P: Serum adhesion molecules and interleukin-2 receptor as markers of tumour load and prognosis in advanced cutaneous melanoma. Eur J Cancer. 37:1629–1634. 2001. View Article : Google Scholar : PubMed/NCBI
20	An X, Li M, Li N, Liu B, Zhang H and Wang J: Effect of heavy-ion beam irradiation on the level of serum soluble interleukin-2 receptors in hamster cheek pouch carcinoma model. Biomed Rep. 2:408–411. 2014. View Article : Google Scholar : PubMed/NCBI
21	Kim KS, Park JM, Kong T, Kim C, Bae SH, Kim HW and Moon J: Retinal angiogenesis effects of TGF-β1 and paracrine factors secreted from human placental stem cells in response to a pathological environment. Cell Transplant. 25:1145–1157. 2016. View Article : Google Scholar : PubMed/NCBI
22	Muller-Pillasch F, Menke A, Yamaguchi H, Elsasser HP, Bachem M, Adler G and Gress TM: TGFbeta and the extracellular matrix in pancreatitis. Hepatogastroenterology. 46:2751–2756. 1999.PubMed/NCBI
23	Yang XJ, Chen GL, Yu SC, Xu C, Xin YH, Li TT, Shi Y, Gu A, Duan JJ, Qian C, et al: TGF-β1 enhances tumor-induced angiogenesis via JNK pathway and macrophage infiltration in an improved zebrafish embryo/xenograft glioma model. Int Immunopharmacol. 15:191–198. 2013. View Article : Google Scholar : PubMed/NCBI
24	Ferrari G, Pintucci G, Seghezzi G, Hyman K, Galloway AC and Mignatti P: VEGF, a prosurvival factor, acts in concert with TGF-beta1 to induce endothelial cell apoptosis. Proc Natl Acad Sci USA. 103:17260–17265. 2006; View Article : Google Scholar : PubMed/NCBI
25	Terme M, Pernot S, Marcheteau E, Sandoval F, Benhamouda N, Colussi O, Dubreuil O, Carpentier AF, Tartour E and Taieb J: VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 73:539–549. 2013. View Article : Google Scholar : PubMed/NCBI
26	Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, Rabie T, Kaden S, Gröne HJ, Hämmerling GJ, et al: Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature. 453:410–414. 2008. View Article : Google Scholar : PubMed/NCBI