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Platelets have been shown to play an important role in systemic and local tumor modulation. Once encountered by tumor cells, platelets are educated to collect and release pro-tumor factors in the tumor/microenvironment, serving as a guiding partner for metastasis. This educational program, however, is not well understood. Here, we show that tumor-educated platelets (TEPs) acquire tumor promoting functions and drive breast cancer progression, metastasis to distal sites including the brain, as well as therapeutic resistance. Importantly, TEPs promoted an increased pro-tumorigenic effect on metastatic breast cancer, compared to their wild-type counterpart, leading to epithelial to mesenchymal transition through NF-κB/STAT3 signaling axis via C/EBPβ transcription factor. Our findings point to the important role of TEPs in breast cancer brain metastasis and therapeutic resistance, which could have a major implication in other tumor types, endorsing TEPs as a potential therapeutic target.

BSCI-04. Tumor-educated platelets promote breast cancer brain metastasis and therapeutic resistance