ResearchVEGF
Genentech Biooncology

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Effects of VEGF in breast cancer beyond angiogenesis

Some investigators have hypothesized that the role of vascular endothelial growth factor (VEGF) in breast cancer is not limited to angiogenesis. Like endothelial cells, breast cancer cells themselves express both VEGF and VEGF receptors (VEGFRs). Thus, breast tumor cells may be able to promote their own growth and avoid apoptosis through VEGF—an autocrine signaling loop. Weigand and colleagues demonstrated that VEGFR-2 is functional on the surface of breast cancer cells. These tumor cell receptors were capable of being stimulated by VEGF, indicating the presence of an autocrine signaling loop distinct from the angiogenic effects of VEGF.22 Mercurio and colleagues have confirmed this finding, hypothesizing that hypoxic conditions select for cells that are capable of autocrine VEGF signaling and that the most aggressive tumor cells are characterized by dependency on VEGF.21

Mercurio and colleagues also proposed that, in addition to antiapoptotic effects, autocrine VEGF signaling may contribute to tumor cell migration and progression.21

  • VEGF165 interacts with NP-1, stimulating antiapoptotic signaling pathways (PI3K/Akt)
  • Semaphorin 3A is a protein that impedes tumor cell migration by binding with NP-1. VEGF165 competes with semaphorin 3A for NP-1 binding, thus blocking its inhibitory effects
  • The integrin α6β4, which can promote the survival of breast cancer cells in stress conditions through the PI3K/Akt pathway, is dependent on VEGF
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Prevalence of VEGF-expressing tumors

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