Journal
CELL BIOLOGY INTERNATIONAL
Volume 40, Issue 11, Pages 1187-1194Publisher
WILEY
DOI: 10.1002/cbin.10656
Keywords
3D culture; 3D spheroid; hypoxia-inducible factor 1 alpha; vascular epithelial growth factor
Categories
Funding
- Keiryokai Research Foundation [9245006]
Ask authors/readers for more resources
In 3D cultured cell systems, the cells form 3D spheroids that mimic cancer cell spheroids in vivo. Cancer cells form cell spheroids as they grow. The in vivo spheroids do not contain a vascular network; therefore, oxygen and nutrition supplies are insufficient. Specifically, the cells in the core region of the cluster are exposed to higher stress levels than the cells in the outer spheroid layer. As a result, the cells in the spheroid are exposed to low nutrition and hypoxia conditions. To overcome these shortages, angiogenesis is induced in cancer spheroids in vivo. Vascular endothelial growth factor (VEGF) is an important molecule involved in angiogenesis. VEGF is secreted by cancer cells in vivo in response to stress conditions such as hypoxia. VEGF expression in cancer cells is mediated by hypoxia-inducible factor 1 alpha (HIF1 alpha), which accumulates in cancer cells during hypoxia. In this report, we show that VEGF expression is regulated by HIF1 alpha and that VEGF is secreted to the outside of the spheroid in vitro. Several investigators have reported that HIF1 alpha forms a protein-protein complex with aryl hydrocarbon receptor translocator (ARNT). We report here that not only HIF1 alpha but also ARNT regulates VEGF expression in 3D cancer spheroids. Our results suggest the utility of the in vitro 3D cancer spheroid model for investigating angiogenesis in cancerous tissues.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available