Endothelial progenitor cells support tumour growth and metastatisation: implications for the resistance to anti-angiogenic therapy.

Abstract

Endothelial progenitor cells (EPCs) have recently been shown to promote the angiogenic switch in solid neoplasms, thereby promoting tumour growth and metastatisation. The genetic suppression of EPC mobilization from bone marrow prevents tumour development and colonization of remote organs. Therefore, it has been assumed that anti-angiogenic treatments, which target vascular endothelial growth factor (VEGF) signalling in both normal endothelial cells and EPCs, could interfere with EPC activation in cancer patients. Our recent data, however, show that VEGF fails to stimulate tumour endothelial colony-forming cells (ECFCs), i.e. the only EPC subtype truly belonging to the endothelial lineage. The present article will survey current evidence about EPC involvement in the angiogenic switch: we will focus on the controversy about EPC definition and on the debate around their actual incorporation into tumour neovessels. We will then discuss how ECFC insensitivity to VEGF stimulation in cancer patients could underpin their well-known resistance to anti-VEGF therapies.

• Authors: Francesco Moccia, Estella Zuccolo, Valentina Poletto, Mariapia Cinelli, Elisa Bonetti, Germano Guerra, Vittorio Rosti
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 9 Pg. 6603-14 (Sep 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26232913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Calcium

Topics

• Calcium (metabolism)
• Drug Resistance, Neoplasm (genetics)
• Endothelial Progenitor Cells (metabolism, pathology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplasms (drug therapy, genetics, pathology)
• Neovascularization, Pathologic (drug therapy, genetics, pathology)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, biosynthesis, genetics)