Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-01, Vol.9 (1), p.107
• Main Authors: Lopes-Coelho, Filipa, Silva, Fernanda, Gouveia-Fernandes, Sofia, Martins, Carmo, Lopes, Nuno, Domingues, Germana, Brito, Catarina, Almeida, António M, Pereira, Sofia A, Serpa, Jacinta
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Aorta - pathology; Blood vessels; Bone marrow; Cancer; CD14 antigen; Cell Differentiation; Cell Line, Tumor; Endothelial cells; endothelial cells (ecs); endothelial progenitor cells (epcs); Endothelial Progenitor Cells - pathology; Endothelium; Female; Flow cytometry; Glutathione; Homeostasis; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Kinases; Laboratory animals; Mice, Inbred BALB C; Mice, SCID; Models, Biological; Monocytes; Monocytes - pathology; Neoplasms - blood supply; Neoplasms - pathology; Neovascularization, Pathologic - pathology; Osteoprogenitor cells; Oxidative stress; Phenotypes; Polymerization; Progenitor cells; Reactive oxygen species; Reactive Oxygen Species - metabolism; Stem cells; Tumor Burden; Tumor microenvironment; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascularization
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9010107

Bone marrow contains endothelial progenitor cells (EPCs) that, upon pro-angiogenic stimuli, migrate and differentiate into endothelial cells (ECs) and contribute to re-endothelialization and neo-vascularization. There are currently no reliable markers to characterize EPCs, leading to their inaccurate identification. In the past, we showed that, in a panel of tumors, some cells on the vessel wall co-expressed CD14 (monocytic marker) and CD31 (EC marker), indicating a putative differentiation route of monocytes into ECs. Herein, we disclosed monocytes as potential EPCs, using in vitro and in vivo models, and also addressed the cancer context. Monocytes acquired the capacity to express ECs markers and were able to be incorporated into blood vessels, contributing to cancer progression, by being incorporated in tumor neo-vasculature. Reactive oxygen species (ROS) push monocytes to EC differentiation, and this phenotype is reverted by cysteine (a scavenger and precursor of glutathione), which indicates that angiogenesis is controlled by the interplay between the oxidative stress and the scavenging capacity of the tumor microenvironment.