Zhang Bing, Wei Chun-Yan, Chang Kai-Kai, Yu Jia-Jun, Zhou Wen-Jie, Yang Hui-Li, Shao Jun, Yu Jin-Jin, Li Ming-Qing, Xie Feng
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China.
Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
Oncol Lett. 2017 Dec;14(6):7483-7488. doi: 10.3892/ol.2017.7121. Epub 2017 Oct 3.
Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor neutralizing antibodies. The results of the tube formation assays revealed that treatment with the supernatant from cervical cancer cells and/or HL-60E resulted in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or TSLPR inhibitors. The results of the present study suggested that TSLP derived of cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by upregulating IL-8 and VEGF production, in a co-culture model between cervical cancer cells and EOS, therefore promoting the development of cervical cancer.
我们之前的研究表明,宫颈癌细胞分泌的胸腺基质淋巴细胞生成素(TSLP)可促进血管生成和细胞募集,并调节嗜酸性粒细胞(EOS)的功能。然而,TSLP在癌症病灶中EOS与血管内皮细胞相互作用中的功能仍不清楚。本研究的目的是探讨TSLP诱导的EOS对人脐静脉内皮细胞(HUVECs)血管生成的影响。本研究结果显示,重组人TSLP蛋白(rhTSLP)可增加HL-60嗜酸性粒细胞(HL-60E)中血管内皮生长因子(VEGF)的分泌,但不增加成纤维细胞生长因子的分泌。与宫颈癌细胞(HeLa或CasKi细胞)或单独的HL-60E相比,宫颈癌细胞与HL-60E细胞共培养体系中白细胞介素(IL)-8和VEGF水平升高。rhTSLP可增强这种效应,但抗人TSLP或TSLP受体中和抗体抑制TSLP信号可减弱这种效应。管形成试验结果显示,用宫颈癌细胞和/或HL-60E的上清液处理可导致HUVECs血管生成增加,TSLP或TSLPR抑制剂可降低这种增加。本研究结果表明,在宫颈癌细胞与EOS的共培养模型中,宫颈癌细胞来源的TSLP可能通过上调IL-8和VEGF的产生间接刺激HUVECs的血管生成,从而促进宫颈癌的发展。