Mechanisms of Vascular Mimicry Impacting Tumor Progression and Response to Therapy in Breast Cancer

Vascular mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with an alternative vascular system that directly connects to host blood vessels whose presence is associated with poor prognosis. However, our molecular understanding of how tumor cells acquire endothelial-like characteristics is relatively poor. Here we show that the transcription factor, Foxc2, promotes VM in breast cancer mouse models by driving ectopic expression of endothelial genes in tumor cells, a process which is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy and suppression of Foxc2 augments response thus motivating the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.