Vasculogenesis: a crucial player in the resistance of solid tumours to radiotherapy

Br J Radiol. 2014 Mar;87(1035):20130686. doi: 10.1259/bjr.20130686.


Tumours have two main ways to develop a vasculature: by angiogenesis, the sprouting of endothelial cells from nearby blood vessels, and vasculogenesis, the formation of blood vessels from circulating cells. Because tumour irradiation abrogates local angiogenesis, the tumour must rely on the vasculogenesis pathway for regrowth after irradiation. Tumour irradiation produces a marked influx of CD11b(+) myeloid cells (macrophages) into the tumours, and these are crucial to the formation of blood vessels in the tumours after irradiation and for the recurrence of the tumours. This process is driven by increased tumour hypoxia, which increases levels of HIF-1 (hypoxia-inducible factor 1), which in turn upregulates SDF-1 (stromal cell-derived factor 1 or CXCL12), the main driver of the vasculogenesis pathway. Inhibition of HIF-1 or of its downstream target SDF-1 prevents the radiation-induced influx of the CD11b(+) myeloid cells and delays or prevents the tumours from recurring following irradiation. Others and we have shown that with a variety of tumours in both mice and rats, the inhibition of the SDF-1/CXCR4 pathway delays or prevents the recurrence of implanted or autochthonous tumours following irradiation or following treatment with vascular disrupting agents or some chemotherapeutic drugs such as paclitaxel. In addition to the recruited macrophages, endothelial progenitor cells (EPCs) are also recruited to the irradiated tumours, a process also driven by SDF-1. Together, the recruited proangiogenic macrophages and the EPCs reform the tumour vasculature and allow the tumour to regrow following irradiation. This is a new paradigm with major implications for the treatment of solid tumours by radiotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / metabolism
  • Female
  • Hypoxia-Inducible Factor 1 / metabolism
  • Male
  • Mice
  • Neoplasms / blood supply*
  • Neoplasms / radiotherapy*
  • Neovascularization, Pathologic / metabolism*
  • Rats
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Stem Cells / metabolism


  • Chemokine CXCL12
  • Hypoxia-Inducible Factor 1
  • Receptors, CXCR4