CXCR4 and breast cancer: (2) Metastasis: in breast cancer, hypoxia and TGF-β1work synergistically to promote secretion of VEGF and stromal derived factor 1 receptor (CXCR4), and inhibition of either the HIF-1α or the TGF-β pathway in tumor cells was shown to decrease bone metastasis and improve survival rates, with no further effect of double blockade, while, unlike molecular blockade, combined drug treatment decreased bone metastases more than either alone [54].