Concise review: Vascular stem cells and tumor angiogenesis

Abstract

Solid tumors are complex "organs" of cancer cells and a heterogeneous population of hematopoietic cells, mesenchymal cells, and endothelial cells. The cancer stem cell model proposes that tumor growth and progression is driven by rare populations of cancer stem cells; however, nontumor-forming stem and progenitor cells are also present within the tumor microenvironment. These adult stem cells do not form tumors when injected into experimental animals, but they may augment tumor growth through juxtacrine and paracrine regulation of tumor cells and by contributing to neovascularization. Thus, cancer cells may actively co-opt nontumor-forming stem cells distally from the bone marrow or proximally from nearby tissue and subvert their abilities to differentiate and maintain tissue growth, repair, and angiogenesis. This review will cover the roles of nontumor-forming vascular stem cells in tumor growth and angiogenesis.

Figure 1

Functions of vascular stem cells in solid tumors. MPC derived from the bone marrow or nearby tissues are a source of VEGF, a potent endothelial cell survival and motility factor. MPC may also differentiate to form pericytes that provide structural support to the nascent vasculature. HPC and their progeny act as “accessory” cells during angiogenesis by expressing tissue remodeling and endothelial survival factors such as MMP9 and VEGF. Similar to MPC, they may provide paracrine instructions to sprouting tip cells during anastomosis. EPC may give rise to ECFC and constitute the primary lumen-forming cells of angiogenic sprouts. ECFC may also provide unique paracrine cues to neighboring “adult” endothelium or the recruited pool of HPC. Taken together, these three populations of progenitors work in concert to form the building blocks of tumor blood vessels. ECFC and MPC form lumens and perivascular cells, respectively, whereas HPC direct and orchestrate vessel sprouting and anastomosis. Abbreviations: EC, endothelial cell; ECFC, endothelial colony-forming cell; EPC, endothelial progenitor cell; HPC, hematopoietic progenitor cell; MPC, mesenchymal progenitor cell; VEGF, vascular endothelial growth factor.