title: 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.affiliation: Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Forlanini 6, 27100, Pavia, Italy. francesco.moccia@unipv.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Moccia
authors.affiliation: Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Forlanini 6, 27100, Pavia, Italy.
authors.forename: Estella
authors.initials: E
authors.lastname: Zuccolo
authors.affiliation: Unit of Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Poletto
authors.affiliation: Department of Public Health, University of Naples "Federico II", via Pansini 5, 80131, Naples, Italy.
authors.forename: Mariapia
authors.initials: M
authors.lastname: Cinelli
authors.affiliation: Unit of Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonetti
authors.affiliation: Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Via F. De Santis, 86100, Campobasso, Italy.
authors.forename: Germano
authors.initials: G
authors.lastname: Guerra
authors.affiliation: Unit of Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
mesh_terms: D002118:Calcium / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002118:Calcium
keywords: Anti-angiogenic therapy; Ca2+ signalling; Endothelial progenitor cells; Patient refractoriness; Renal cellular carcinoma; Tumour vascularisation; Vascular endothelial growth factor