Role of bone marrow-derived cells in angiogenesis: focus on macrophages and pericytes.

Tumor growth relies on the formation of new blood vessels to receive an adequate supply of oxygen and nutrient. This process is facilitated by both the remodeling of the pre-existing vasculatures and the recruitment of the progenitor/stem cells originated from bone marrow-derived cells (BMDCs). Evidences from both animal studies and human trials have reported that these tumor-associated BMDCs differentiate into a series of stromal cells including macrophages and pericytes, and regulate tumor angiogenesis in various aspects. Macrophages constitute a large portion of the BMDCs infiltrated in the tumor microenvironment, and have been shown to disrupt the balance of pro- and anti-angiogenic signalings by the secretion of various cytokines. Pericytes, mainly derived from the subpopulation of PDGFRβ(+) BMDCs, can provide both pro-survival signaling and mechanical support to maintain the newly formed endothelium via the direct interactions with endothelial cells. In the current review, we summarize the recruitment mechanisms of BMDC-derived macrophages and pericytes within tumor microenvironment, and also review the contribution of these cells to the different aspects of angiogenesis, with particular emphasis on their therapeutic implications as potential targets for anti-tumor strategies.