The tumor microenvironment has been shown to be deeply affected by myeloid cells, including CD11b+Gr1+ cells, which are able to produce soluble factors, such as Bv8, that influence angiogenesis, extracellular matrix remodeling, anti-VEGF resistance and mobilization of additional myeloid cells toward premetastatic sites [44]. This evidence concerns the gene PROK2 and neoplasm.