Macrophages enhance Vegfa-driven angiogenesis in an embryonic zebrafish tumour xenograft model
- Britto, D.D., Wyroba, B., Chen, W., Lockwood, R.A., Tran, K.B., Shepherd, P.R., Hall, C.J., Crosier, K.E., Crosier, P.S., Astin, J.W.
- Disease models & mechanisms 11(12): (Journal)
- Registered Authors
- Astin, Jonathan, Crosier, Kathy, Crosier, Phil
- Angiogenesis, Macrophage, Tumour, Xenograft, Zebrafish
- MeSH Terms
- Cell Line, Tumor
- Embryo, Nonmammalian/pathology*
- Neoplasms/blood supply*
- Neovascularization, Pathologic/metabolism*
- Vascular Endothelial Growth Factor A/metabolism*
- Xenograft Model Antitumor Assays*
- Zebrafish Proteins/metabolism*
- 30396905 Full text @ Dis. Model. Mech.
Britto, D.D., Wyroba, B., Chen, W., Lockwood, R.A., Tran, K.B., Shepherd, P.R., Hall, C.J., Crosier, K.E., Crosier, P.S., Astin, J.W. (2018) Macrophages enhance Vegfa-driven angiogenesis in an embryonic zebrafish tumour xenograft model. Disease models & mechanisms. 11(12):.
Tumour angiogenesis has long been a focus of anti-cancer therapy, however, anti-angiogenic cancer treatment strategies have had limited clinical success. Tumour-associated myeloid cells are believed to play a role in the resistance of cancer towards anti-angiogenesis therapy, but the mechanisms by which they do this are unclear. A zebrafish embryonic xenograft model has been developed to investigate the mechanisms of tumour angiogenesis and as an assay to screen anti-angiogenic compounds. In this study, we used cell ablation techniques to remove either macrophages or neutrophils and assessed their contribution towards zebrafish xenograft angiogenesis by quantitating levels of graft vascularisation. The ablation of macrophages, but not neutrophils, caused a strong reduction in tumour xenograft vascularisation and time-lapse imaging demonstrated that tumour xenograft macrophages directly associated with the migrating tip of developing tumour blood vessels. Finally, we found that while macrophages are required for vascularisation in xenografts that either secrete VEGFA or overexpress zebrafish vegfaa, they are not required for the vascularisation of grafts with low levels of VEGFA, suggesting that zebrafish macrophages can enhance Vegfa-driven tumour angiogenesis. The importance of macrophages to this angiogenic response suggests that this model could be used to further investigate the interplay between myeloid cells and tumour vascularisation.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes