Activated platelets facilitate hematogenous metastasis of breast cancer by modulating the PDGFR-β/COX-2 axis.

Platelets have been widely recognized as a bona fide mediator of malignant diseases, and they play significant roles in influencing various aspects of tumor progression. Paracrine interactions between platelets and tumor cells have been implicated in promoting the dissemination of malignant cells to distant sites. However, the underlying mechanisms of the platelet-tumor cell interactions for promoting hematogenous metastasis are not yet fully understood. We found that activated platelets with high expression of CD36 were prone to release a plethora of growth factors and cytokines, including high levels of PDGF-B, compared to resting platelets. PDGF-B activated the PDGFR-β/COX-2 signaling cascade, which elevated an array of pro-inflammatory factors levels, thereby aggravating tumor metastasis. The collective administration of CD36 inhibitor and COX-2 inhibitor resolved the interactions between platelets and tumor cells. Collectively, our findings demonstrated that targeting the crosstalk between platelets and tumor cells offers potential therapeutic strategies for inhibiting tumor metastasis.