CCL2 and metastatic malignant neoplasm: ZTX models have also been used extensively in basic, molecular cancer research for example to identify a hypoxia-induced VEGF-VEGFR2 signaling pathway that drove metastatic dissemination of fibrosarcoma cells [47], the pro-metastatic signaling by CCL2 and CCL5 between ER-positive breast cancer tumor cells and infiltrating macrophages [17], and the capability of CAFs isolated from metastatic cancers to educate non-invasive tumor cells to become metastatic [16].