Paclitaxel treatment enhances lymphatic metastasis of B16F10 melanoma cells via CCL21/CCR7 axis

Int J Biol Sci. 2022 Jan 24;18(4):1476-1490. doi: 10.7150/ijbs.67138. eCollection 2022.

Abstract

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

Keywords: B16F10; CCL21/CCR7 axis; Cell migration; Chemotherapy; Lymphatic metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CCL21* / metabolism
  • Chemokine CCL21* / pharmacology
  • Ligands
  • Lymphatic Metastasis
  • Melanoma* / drug therapy
  • Mice
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Receptors, CCR7 / metabolism

Substances

  • Ccr7 protein, mouse
  • Chemokine CCL21
  • Ligands
  • Receptors, CCR7
  • Paclitaxel