Researchers from The Scripps Research Institute (CA, USA) have identified for the first time a role for macrophages in the structural formation of vascular mimicry networks in both tumor and angiogenesis in vivo models. The findings, published recently in Nature Scientific Reports, may provide novel therapeutic targets for cancer.
Macrophages were previously thought to only play a supportive role in angiogenesis, through cytokine secretion and remodelling of the extracellular matrix. In this study, researchers demonstrated for the first time that macrophages play a key role in the formation of nonendothelial-derived vessel-like networks.
These nonendothelial networks, termed vascular mimicry, have been observed in a range of solid tumors including glioblastoma, breast cancer, lung cancer and melanoma.
The team demonstrated that macrophages interact with the angiogenic front of invading endothelial blood vessels and express extracellular matrix degrading proteases to form a vascular mimicry network. This primitive network expresses both macrophage and endothelial markers and is connected to systemic vasculature.
The team also highlighted that hypoxia is an important mediator in the formation of the vascular mimicry network, with the conditional deletion of hypoxia-inducible factor 1α resulting in a decrease in network formation and tumor growth.
The researcher’s results may shed light on why some cancer drugs which are designed to slow angiogenesis are not effective for all patients. Lead author Martin Friedlander (The Scripps Research Institute) commented: “This may represent a whole new therapeutic target for treating tumors.”
Sources: Barnett FH, Rosenfeld M, Wood M et al; Macrophages form functional vascular mimicry channels in vivo Sci. Rep. 10.1038/srep36659 (2016); The Scripps Research Institute press release