PUBLICATION
Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism
- Authors
- Zhao, C., Zhang, W., Zhao, Y., Yang, Y., Luo, H., Ji, G., Dong, E., Deng, H., Lin, S., Wei, Y., Yang, H.
- ID
- ZDB-PUB-160115-9
- Date
- 2016
- Source
- Scientific Reports 6: 19404 (Journal)
- Registered Authors
- Yang, Yun
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Proliferation/drug effects
- Disease Models, Animal
- Endothelial Cells/metabolism*
- Endothelium, Vascular/metabolism
- Heterografts
- Interleukin-8/metabolism
- Interleukin-8/pharmacology
- Lung Neoplasms/secondary
- Melanoma, Experimental
- Mice
- Neoplasms/metabolism*
- Neoplasms/pathology*
- Neovascularization, Pathologic/metabolism*
- Paracrine Communication*
- Tumor Burden
- Tumor Microenvironment
- Zebrafish
- PubMed
- 26762853 Full text @ Sci. Rep.
Citation
Zhao, C., Zhang, W., Zhao, Y., Yang, Y., Luo, H., Ji, G., Dong, E., Deng, H., Lin, S., Wei, Y., Yang, H. (2016) Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism. Scientific Reports. 6:19404.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping