For instance, osteotropic BC MCF-7 cells cultured in 3D Matrigel have increased expression of VEGF, bFGF and IL-8, which are the main mediators of endothelial cell recruitment and differentiation and thus promote angiogenesis.64 Culturing endothelial cells on collagen matrices with cancer cells and fibroblasts leads to the formation of branching microvasculature, indicating that cancer cells and fibroblasts embedded in collagen can trigger migration and differentiation of endothelial cells with elevated expression of VEGF.60,65. Here, VEGFA is linked to breast cancer.