Targeting angiogenesis:
Inhibition of a tumor’s lifeline

Angiogenesis is a vital process that facilitates tumor growth and survival.^1-3 Tumor angiogenesis refers to the ability of a tumor to stimulate new blood vessel formation.^1,2 This critical step in development enables tumor expansion, local invasion, and dissemination through^1-3:

• Delivery of oxygen, nutrients, and survival factors
• Production of growth factors that benefit tumor cells
• Formation of a route for tumor cell egress

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Angiogenesis is a well-controlled process that is regulated by angiogenic, growth, and survival factors that are secreted by the malignant cells as well as other cells within the tumor microenvironment.^2,4

The process of sprouting angiogenesis is regulated by many extracellular factors, including EGF-like domain-containing protein 7 (EGFL7), a protein expressed by endothelial cells.^5-8 EGFL7 is associated with the extracellular matrix and is upregulated in many proliferative tissues, including tumors.^6-8 EGFL7 supports endothelial cell adhesion and vascular tube formation by defining an efficient migratory path for endothelial cells.⁸ Furthermore, it also protects endothelial cells that are under biological stress, another pro-survival mechanism.⁹

References:

1.

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.

2.

Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401-410.

3.

Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011-1027.

4.

Nyberg P, Salo T, Kalluri R. Tumor microenvironment and angiogenesis. Front Biosci. 2008;13:6537-6553.

5.

Schmidt M, Paes K, De Mazière A, et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development. 2007;134:2913-2923.

6.

Campagnolo L, Leahy A, Chitnis S, et al. EGFL7 is a chemoattractant for endothelial cells and is up-regulated in angiogenesis and arterial injury. Am J Pathol. 2005;167:275-284.

7.

Fitch MJ, Campagnolo L, Kuhnert F, Stuhlmann H. Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial cells. Dev Dyn. 2004;230:316-324.

8.

Parker LH, Schmidt M, Jin S-W, et al. The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature. 2004;428:754-758.

9.

Xu D, Perez RE, Ekekezie II, Navarro A, Truog WE. Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxia-induced cell death. Am J Physiol Lung Cell Mol Physiol. 2008;294:L17-L23.