TAMI-07. TUMOR-EDUCATED PLATELETS GUIDE BREAST CANCER BRAIN METASTASIS AND PROMOTE THERAPEUTIC RESISTANCE

Abstract

Abstract BACKGROUND 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. METHODS Wild-type platelets (WTPs) were isolated from blood of healthy humans or mice, whereas tumor-educated platelets (TEPs) were isolated from blood of breast cancer patients or from tumor-bearing donor mice. The tumorigenic and modulatory effect of these two types of platelets on breast cancer was examined in-vitro and in-vivo. RESULTS Here, we show that TEPs acquire tumor promoting functions and drive breast cancer progression, metastasis to distal sites specifically 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, promoting epithelial to mesenchymal transition through NF-κB/STAT3 signaling axis via C/EBPβ transcription factor. CONCLUSION 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.