title: Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism.
abstract: The angiogenic switch is an important oncogenic step that determines whether microtumors remain dormant or progresses further. It has been generally perceived that the primary function of this tumorgenic event is to supply oxygen and nutrients through blood circulation. Using in vivo imaging of zebrafish and mouse tumor models, we showed that endothelial cords aggressively penetrated into microtumors and remained non-circulatory for several days before undergoing vascular blood perfusion. Unexpectedly, we found that initial tumor growth in both models was significantly reduced if endothelial cords were removed by blocking VEGF-VEGFR2 signaling or using a vascular deficient zebrafish mutant. It was further shown that soluble factors including IL-8, secreted by endothelial cells (ECs) were responsible for stimulating tumor cells proliferation. These findings establish that tumor angiogenesis play a much earlier and broader role in promoting tumor growth, which is independent of vascular circulation. Understanding this novel mechanism of angiogenic tumor progression offers new entry points for cancer therapeutics.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Chengjian
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Gaili
authors.initials: G
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: E
authors.initials: E
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.|Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Hanshuo
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D064593:Heterografts; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D019899:Paracrine Communication; D047368:Tumor Burden; D059016:Tumor Microenvironment; D015027:Zebrafish
chemical_list: D016209:Interleukin-8