Paclitaxel treatment enhances lymphatic metastasis of B 16 F 10 1 melanoma cells via CCL 21 / CCR 7 axis 2

22 Chemotherapeutic drugs have been successfully used to treat several 23 cancers, including melanoma. However, metastasis occasionally occurs 24 after chemotherapy. Here, we reported that paclitaxel (PTX) treatment for 25 B16F10 tumour in mice led to an enhanced lymphatic metastasis of the 26 melanoma cells, although a significant inhibition of tumour growth at the 27 injection site was observed. Further study demonstrated that PTX 28 upregulated the expression of C-C chemokine receptor type 7 (CCR7) in 29 B16F10 cells, enhancing their migration through the activation of JNK 30 and p38 signalling pathways. Loss of CCR7 or blockade of C-C motif 31 chemokine ligand 21 (CCL21)/CCR7 axis abolished the pro-migration 32 effect of PTX on B16F10 melanoma cells. Importantly, combination of 33 PTX and CCR7 mAb could simultaneously delay the tumour growth and 34 reduce the lymphatic metastasis in B16F10 melanoma. The blockade of 35 CCL21/CCR7 axis may collectively serve as a strategy for lymphatic 36 metastasis in some melanoma after chemotherapy. 37