The podoplanin-CLEC-2 interaction promotes platelet-mediated melanoma pulmonary metastasis

BMC Cancer. 2024 Apr 1;24(1):399. doi: 10.1186/s12885-024-12194-w.

Abstract

Background: Podoplanin (PDPN) expressed on tumour cells interacts with platelet C-type lectin-like receptor 2 (CLEC-2). This study aimed to investigate the role of the PDPN-platelet CLEC-2 interaction in melanoma pulmonary metastasis.

Methods: Murine melanoma B16-F0 cells, which have two populations that express podoplanin, were sorted by FACS with anti-podoplanin staining to obtain purified PDPN + and PDPN- B16-F0 cells. C57BL/6J mice transplanted with CLEC-2-deficient bone marrow cells were used for in vivo experiments.

Results: The in vivo data showed that the number of metastatic lung nodules in WT mice injected with PDPN + cells was significantly higher than that in WT mice injected with PDPN- cells and in WT or CLEC-2 KO mice injected with PDPN- cells. In addition, our results revealed that the platelet Syk-dependent signalling pathway contributed to platelet aggregation and melanoma metastasis.

Conclusions: Our study indicates that the PDPN-CLEC-2 interaction promotes experimental pulmonary metastasis in a mouse melanoma model. Tumour cell-induced platelet aggregation mediated by the interaction between PDPN and CLEC-2 is a key factor in melanoma pulmonary metastasis.

Keywords: CLEC-2; Melanoma; Platelet aggregation; Podoplanin; Pulmonary metastasis.

MeSH terms

  • Animals
  • Blood Platelets / metabolism
  • Lectins, C-Type / metabolism
  • Lung Neoplasms* / metabolism
  • Melanoma* / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Platelet Aggregation

Substances

  • CLEC-2 protein, mouse
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Gp38 protein, mouse