JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (2): 38-43.doi: 10.6040/j.issn.1671-7554.0.2015.798

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Breast tumor deriving VEGF induces vascular endothelial cells to suppress immune functions

LI Ranran, ZHANG Pengfei, YUAN Bing, FANG Feifei, HAN Mingyong   

  1. Cancer Therapy and Research Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2015-08-22 Online:2016-02-10 Published:2016-02-10

Abstract: Objective To explore the effect of breast tumor deriving vascular endothelial growth factor(VEGF)on the immune functions of vascular endothelial cells(VEC). Methods Human umbilical vein endothelial cells(HUVEC)were divided into 4 groups: Media group, T-sup group, VEGF group and SU5416 group. The levels of VEGF, PGE2, IL-6 and IL-12 in 24 h conditioned cultural supernatants were assayed by ELISA. Experiments of CCK-8, ELISPOT and flow cytometry were processed on peripheral blood T cells after treatment with the 24 h conditioned cultural supernatants. Results The levels of VEGF, PGE2 and IL-6 were increased in the T-sup group, compared with those in Media group(P<0.05), and the level of IL-12 was decreased in the T-sup group(P<0.05). Compared with Media group, the conditioned media in T-sup group promoted the apoptosis of T-lymphocytes, suppressed the expression of IFN-γ, and reduced the production of IFN-γ in CD8+ T cells. The levels of VEGF, PGE2 and IL-6 were increased and the level of IL-12 was decreased in the VEGF group, compared with those in Media group. But there were no statistically significant differences after the treatment of SU5416, a VEGF receptor antagonist. Conclusion Breast tumor cells suppress the immune fuctions of VEC, which is closely related with the high expression of VEGF.

Key words: Breast cancer, Vascular endothelial cells, Immune suppression, Vascular endothelial growth factor

CLC Number: 

  • R737.9
[1] Lorusso G, Ruegg C. New insights into the mechanisms of organ-specific breast cancer metastasis[J]. Seminars in Cancer Biology, 2012, 22(3):226-233.
[2] Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation[J]. Cell, 2011, 144(5):646-674.
[3] Khan H, Gucalp R, Shapira I. Evolving concepts: immunity in oncology from targets to treatments[J]. J Oncol, 2015, doi:10.1155/2015/847383. Epub 2015 Apr 28.
[4] Mulligan JK, Young MR. Tumors induce the formation of suppressor endothelial cells in vivo[J]. Cancer Immunol Immunother, 2010, 59(2):267-277.
[5] 黄秀英, 陈智超. 肿瘤血管内皮细胞介导肿瘤免疫逃逸的机制[J]. 国际输血及血液学杂志, 2012, 35(1):78-80. HUANG Xiuying, CHEN Zhichao. The mechanism of tumor vascular endothelial cell mediated tumor immune escape[J]. Int J Blood Transfus Hemato, 2012, 35(1):78-80.
[6] Puddey IB, Zilkens RR, Croft KD, et al. Alcohol and endothelial function:a brief review[J]. Clin Exp Pharmacol Physiol, 2001, 28(12):1020-1024.
[7] Nieves Torres EC, Yang B, Brahmbhatt A, et al. Blood outgrowth endothelial cells reduce hypoxia-mediated fibroblast to myofibroblast conversion by decreasing proangiogenic cytokines[J]. J Vasc Res, 2014, 51(6):458-467.
[8] Hsu JY, Chang KY, Chen SH, et al. Epidermal growth factor-induced cyclooxygenase-2 enhances head and neck squamous cell carcinoma metastasis through fibronectin up-regulation [J]. Oncotarget, 2015, 6(3):1723-1739.
[9] 张煊, 曹雪涛. 肿瘤免疫逃逸机制研究新进展[J]. 中国肿瘤生物治疗杂志, 2001, 8(1):72-74. ZHANG Xuan, CAO Xuetao. The new progressment of mechanism of tumor immune escape[J]. Chin J Cancer Biother, 2001, 8(1):72-74.
[10] Fearnley GW, Smith GA, Odell AF, et al. Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells[J]. Methods Enzymol, 2014, 535:265-292.
[11] Raikwar NS, Liu KZ, Thomas CP. N-terminal cleavage and release of the ectodomain of Flt1 is mediated via ADAM10 and ADAM17 and regulated by VEGFR2 and the Flt1 intracellular domain[J]. PLoS One, 2014, 9(11):e112794. doi:10.1371/journal.pone.0112794.
[12] Han FH, Li HM, Zheng DH, et al. The effect of the expression of vascular endothelial growth factor(VEGF)-C and VEGF receptor-3 on the clinical outcome in patients with gastric carcinoma[J]. Eur J Surg Oncol, 2010, 36(12):1172-1179.
[13] Winiarski BK, Wolanska KI, Rai S, et al. Epithelial ovarian cancer-induced angiogenic phenotype of human omental microvascular endothelial cells may occur independently of VEGF signaling [J]. Transl Oncol, 2013, 6(6):703-714.
[14] 徐晓娅, 毕玉莉, 姜曼, 等. 血管内皮生长因子促进肺转移相关受体通路的研究[J]. 山东大学学报(医学版), 2013, 51(11):25-29. XU Xiaoya, BI Yuli, JIANG Man, et al. Vascular endothelial growth factor(VEGF)promotes lung carcinoma metastasis via VEGFR1 in mouse model[J]. Journal of Shandong University(Health Sciences), 2013, 51(11):25-29.
[15] Tamura K, Sakurai T, Kogo H. Relationship between prostagland in E2 and vascular endothelial growth factor(VEGF)in angiogenesis in human vascular endothelial cells[J]. Vascul Pharmacol, 2006, 44(6):411-416.
[16] Pockaj BA, Basu GD, Pathangey LB, et al. Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer[J]. Ann Surg Oncol, 2004, 11(3):328-339.
[17] Mulligan J, Lathers D, Young M. Tumors skew endothelial cells to disrupt NK cell, T-cell and macrophage functions[J]. Cancer Immunol Immunother, 2008, 57(7):951-961.
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