Adrenergic signaling promotes angiogenesis through endothelial cell-tumor cell crosstalk

被引:63
作者
Chen, Hongyu [1 ]
Liu, Dan [1 ]
Yang, Zhengyan [1 ]
Sun, Limin [1 ]
Deng, Que [1 ]
Yang, Shuo [1 ]
Qian, Lu [1 ]
Guo, Liang [1 ]
Yu, Ming [1 ]
Hu, Meiru [1 ]
Shi, Ming [1 ]
Guo, Ning [1 ]
机构
[1] Inst Basic Med Sci, Dept Pathophysiol, Beijing 100850, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
catecholamine; beta; 2-AR; Jagged; 1; Notch; angiogenesis; breast cancer; BREAST-CANCER; NOTCH; EXPRESSION; GROWTH; VEGF; ACTIVATION; PATHWAYS; JAG1; INVASIVENESS; METASTASIS;
D O I
10.1530/ERC-14-0236
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Angiogenesis is an important factor in invasive tumor growth, progression, and metastasis. Multiple proangiogenic mechanisms are involved in tumor angiogenesis. In this study, we showed that the neurotransmitter norepinephrine upregulated VEGF (VEGFA) expression in breast cancer cells and that the culture supernatant from norepinephrine-treated breast cancer cells promoted the formation of the capillary-like network of endothelial cells. However, the effects of norepinephrine were further enhanced when the endothelial cells were cocultured with breast cancer cells, indicating a critical role of tumor cell-endothelial cell contacts in norepinephrine-induced tumor angiogenesis. Interestingly, norepinephrine dramatically induced the activation of the Notch pathway, which is a cell-contact-mediated intercellular signaling pathway and tightly linked to tumor cell-stromal cell interaction and angiogenesis, in the endothelial cells that had been cocultured with breast cancer cells. Furthermore, the expression of the Notch ligand Jagged 1 was significantly upregulated by norepinephrine at both mRNA and protein levels in breast cancer cells. Inhibitors of beta 2-adrenergic receptor (beta 2-AR), protein kinase A (PKA), and mTOR could reverse norepinephrine-induced Jagged 1 upregulation, indicating that the beta 2-AR-PKA-mTOR pathway participates in this process. Knockdown of Jagged 1 expression in breast cancer cells not only repressed norepine-phrine-induced activation of the Notch pathway in cocultured endothelial cells but also evidently impaired the effects of norepinephrine on capillary-like sprout formation. These data demonstrate that tumor angiogenesis mediated by the Jagged 1/Notch intercellular signaling is governed by the norepinephrine-activated beta 2-AR-PKA-mTOR pathway.
引用
收藏
页码:783 / 795
页数:13
相关论文
共 50 条
  • [31] Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling
    Liu, Yang
    Li, Fan
    Gao, Feng
    Xing, Lingxi
    Qin, Peng
    Liang, Xingxin
    Zhang, Jiajie
    Qiao, Xiaohui
    Lin, Lizhou
    Zhao, Qian
    Du, Lianfang
    ONCOTARGET, 2016, 7 (26) : 40148 - 40159
  • [32] RUNX1 promotes angiogenesis in colorectal cancer by regulating the crosstalk between tumor cells and tumor associated macrophages
    Guo, Xuxue
    Zhang, Haonan
    He, Chengcheng
    Qin, Kaiwen
    Lai, Qiuhua
    Fang, Yuxin
    Chen, Qianhui
    Li, Weize
    Wang, Yiqing
    Wang, Xinke
    Li, Aimin
    Liu, Side
    Li, Qingyuan
    BIOMARKER RESEARCH, 2024, 12 (01)
  • [33] B7-H3 modulates endothelial cell angiogenesis through the VEGF cytokine
    Lai, Huijun
    Sun, Zhongwen
    Yang, Jie
    Wu, Pingping
    Guo, Yundi
    Sun, Jing
    IMMUNOLOGIC RESEARCH, 2019, 67 (2-3) : 202 - 211
  • [34] Chlamydia pneumoniae infection promotes vascular endothelial cell angiogenesis through an IQGAP1-related signaling pathway
    Wang, Beibei
    Zhang, Lijun
    Liu, Jingya
    Ma, Lu
    Wang, Haiwei
    Zheng, Ningbo
    Chen, Xiaoyu
    Shen, Bingling
    Xu, Zhelong
    Zhang, Lijun
    INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 2017, 307 (4-5) : 276 - 286
  • [35] Aquaporin 5 promotes tumor migration and angiogenesis in non-small cell lung cancer cell line H1299
    Elkhider, Abdalkhalig
    Wang, Bing
    Ouyang, Xunli
    Al-Azab, Mahmoud
    Walana, Williams
    Sun, Xiaotong
    Li, Han
    Tang, Yawei
    Wei, Jing
    Li, Xia
    ONCOLOGY LETTERS, 2020, 19 (03) : 1665 - 1672
  • [36] The Passenger Domain of Bartonella bacilliformis BafA Promotes Endothelial Cell Angiogenesis via the VEGF Receptor Signaling Pathway
    Tsukamoto, Kentaro
    Kumadaki, Kayo
    Tatematsu, Kaoru
    Suzuki, Natsumi
    Doi, Yohei
    MSPHERE, 2022, 7 (02)
  • [37] Mast cell-tumor cell interactions: For or against tumour growth and metastasis?
    Dimitriadou, V
    Koutsilieris, M
    ANTICANCER RESEARCH, 1997, 17 (3A) : 1541 - 1549
  • [38] Alcohol promotes mammary tumor growth through activation of VEGF-dependent tumor angiogenesis
    Lu, Yanmin
    Ni, Fang
    Xu, Mei
    Yang, Jinlian
    Chen, Ji
    Chen, Zhuo
    Wang, Xinyi
    Luo, Jia
    Wang, Siying
    ONCOLOGY LETTERS, 2014, 8 (02) : 673 - 678
  • [39] Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function
    Ikeda, Yasumasa
    Tajima, Soichiro
    Yoshida, Sumiko
    Yamano, Noriko
    Kihira, Yoshitaka
    Ishizawa, Keisuke
    Aihara, Ken-ichi
    Tomita, Shuhei
    Tsuchiya, Koichiro
    Tamaki, Toshiaki
    ATHEROSCLEROSIS, 2011, 215 (02) : 339 - 347
  • [40] Hedgehog signaling in myofibroblasts directly promotes prostate tumor cell growth
    Domenech, Maribella
    Bjerregaard, Robert
    Bushman, Wade
    Beebe, David J.
    INTEGRATIVE BIOLOGY, 2012, 4 (02) : 142 - 152