VEGFA and neoplasm: Thus, osteoblasts participate in a “vicious cycle” between tumor cells and the bone microenvironment, whereby the destruction of the bone microenvironment and tumor cell proliferation promote each other by releasing vascular endothelial growth factor-(VEGF), matrix metalloproteinases (MMPs), thrombospondin, and inflammatory and coagulation factors (Hirshberg et al., 2014; Wang et al., 2015).