Specific chemotherapeutic agents induce metastatic behaviour through stromal- and tumour-derived cytokine and angiogenic factor signalling.

摘要: Recent studies reveal that chemotherapy can enhance metastasis due to host responses, such as augmented expression of adhesion molecules in endothelial cells and increased populations myeloid cells. However, it is still unclear how tumour contribute this process. Here, we observed paclitaxel carboplatin accelerated lung tumour-bearing mice, while doxorubicin fluorouracil did not. Mechanistically, induced similar changes cytokine angiogenic factors. Increased levels CXCR2, CXCR4, S1P/S1PR1, PlGF PDGF-BB were identified the serum or primary tissues mice treated by paclitaxel. The CXCL1 tissue level CXCR4 also elevated carboplatin. On other hand, not induce changes. chemotherapy-induced factor confirmed gene datasets from human patients following treatment. These chemotherapy-enhanced cytokines factors further angiogenesis, destabilized vascular integrity, recruited BMDCs metastatic organs mediated proliferation, migration epithelial-to-mesenchymal transition Interestingly, inhibitors these counteracted both normal injected intravenously with B16F10-GFP In particular, blockade SDF-1α-CXCR4 S1P-S1PR1 axes only compromised but prolonged median survival time 33.9% 40.3%, respectively. current study delineates mechanism provides novel therapeutic strategies counterbalance pro-metastatic effects chemo-drugs via combination treatment anti-cytokine/anti-angiogenic therapy.