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Effects of VEGF in breast cancer beyond angiogenesis

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

 

Mercurio and colleagues also proposed that, in addition to anti-apoptotic effects, autocrine VEGF signalling may contribute to cancer cell migration and progression22

  • VEGF165 interacts with NP-1, stimulating anti-apoptotic signalling pathways (PI3K/Akt).
  • Semaphorin 3A is a protein that impedes tumour 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.