Myeloid cell trafficking and tumor angiogenesis

Abstract

Tumor growth and metastasis depend on neovascularization, the growth of new blood vessels. Recent findings have revealed that tumor neovascularization is regulated in part by monocytes, which are myeloid lineage cells from the bone marrow. Tumors exhibit significant monocyte infiltrates, which are actively recruited to the tumor microenvironment. Upon tumor infiltration, monocytes can participate in tumor neovascularization. Monocytes can either differentiate into macrophages, which express proangiogenic growth factors, or into endothelial-like cells, which may directly participate in neovascularization. Preliminary studies in animals suggest that modulation of bone marrow-derived cell trafficking into tumors will provide a useful new approach in cancer therapy.

Figure 1. Bone marrow derived myeloid cells contribute to tumor angiogenesis

Myeloid precursor cells adhere to angiogenic endothelium via activated α4β1 or β2 integrins. Stromal derived growth factor 1 (SDF-1), colony stimulating factors (GM-CSF and others) or β-defensin mobilize specific subsets of myeloid precursor cells. In the presence of specific cytokines and growth factors, these cells differentiate either into endothelial-like cells, which are directly incorporated into new blood vessels (green arrow), or into monocytes / macrophages, which support tumor growth in a indirect manner (blue arrow). While interleukin-10 promotes differentiation of monocytes into M2 macrophages, VEGF and other factors promote endothelial cell differentiation from progenitor cells.