C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells

摘要: Increasing evidence suggests that myeloid bone marrow-derived cells (BMDCs) play a critical role in lung metastasis. Blockade of VEGF receptor 1 (VEGFR1) has been proposed as potential strategy to limit BMDC recruitment tumors. However, preclinical indicates this may not be effective all Thus, establishing which molecular mechanisms are responsible for the “escape” these BMDCs from VEGFR1 inhibition would facilitate development strategies control Here, we report complementary chemokine (C-X-C motif) ligand 12/C-X-C 4 (CXCR4) and VEGF/VEGFR1 pathways promoting metastasis mice via using chimeric with deficiency CXCR4 VEGFR1–tyrosine kinase BMDCs. We first demonstrate activity is essential differentiation antigen (Gr-1)-positive BMDCs, whereas macrophage established Inhibition both signaling exerted greater effects on tumor vascular density, growth, than alone. These were reproduced after pharmacologic AMD3100. independently promigratory effect by activating p38 mitogen-activating protein kinase. combining blockade induce growth delay prevent or inhibit