Figure 1.

Vascular endothelial growth factor-A in endothelial cells and breast cancer stem cells promote breast cancer progression and metastasis. VEGF receptors are expressed in both endothelial cells and breast cancer stem cells. Endothelial cells form endothelium with tight cell–cell junction. Effects of VEGF on endothelial cells include cell survival, permeability, cell proliferation, and cell migration. VEGF also plays an important role in breast cancer cell migration and cancer stem cell self-renewal. These functions converge on promoting breast cancer progression and metastasis. Endothelial cells will be attracted and activated by high levels of VEGF proteins in the tumor-stromal niche. After endothelial cells form new blood vessels surrounding tumor cells, tumor cells will be stimulated by the cytokines in the blood supply. Tumor cells go through epithelial-to-mesenchymal transition, intravasation, circulation, extravasation, and finally form distal metastases.