Tumor Angiogenesis and the VEGF Pathway

Angiogenesis: a necesary part of the process in the progression of cancer

Figure 1. Tumor angiogenesis

VEGF and tumor angiogenesis image

Angiogenesis is a hallmark of tumor development

Angiogenesis is a necessary part of the process in the progression of cancer from small, localized neoplasms to larger, growing, and potentially metastatic tumors. To grow beyond 1 to 2 mm in diameter, a tumor needs an independent blood supply, which is acquired by the expression of growth factors that recruit new vasculature from existing blood vessels (Figure 1). This process continues even as the tumor matures. Thus, upregulation of angiogenesis is a key step in sustained tumor growth and may also be critical for tumor metastasis.1-4

VEGF is a regulator of tumor angiogenesis

VEGF (also known as VEGF-A, but commonly referred to simply as VEGF) stands for "vascular endothelial growth factor." As its name suggests, VEGF stimulates vascular endothelial cell growth, survival, and proliferation.2

VEGF is a member of a family of 6 structurally related proteins (Table 1) that regulate the growth and differentiation of multiple components of the vascular system, especially blood and lymph vessels. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2.1,2,5,6

Table 1. The VEGF protein family1-3

VEGF ligands Receptors Functions
VEGF (VEGF-A) VEGFR-1, VEGFR-2, neuropilin-1 Angiogenesis
Vascular maintenance
VEGF-B VEGFR-1 Not established
VEGF-C VEGFR-2, VEGFR-3 Lymphangiogenesis
VEGF-D VEGFR-2, VEGFR-3 Lymphangiogenesis
VEGF-E (viral factor) VEGFR-2 Angiogenesis
Placental growth factor VEGFR-1, neuropilin-1 Angiogenesis

The VEGF signaling pathway

VEGF ligands mediate their angiogenic effects by binding to specific VEGF receptors, leading to subsequent signal transduction.1,2

1 Upstream activators stimulate the production of VEGF.
2 VEGF binds to receptors on endothelial cells.
3 Angiogenesis is mediated primarily through the interaction of VEGF-A with VEGFR-2.
4 Other variants of the VEGF ligand and receptor play a secondary role in this process.


  1. Ferrara N. Endocr Rev. 2004;25:581-611. PMID: 15294883
  2. Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027. PMID: 15585754
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  4. Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410. PMID: 12778130
  5. Relf M, LeJeune S, Scott PA, et al. Cancer Res. 1997;57:963-969. PMID: 9041202
  6. Stimpfl M, Tong D, Fasching B, et al. Clin Cancer Res. 2002;8:2253-2259. PMID: 12114428