STEM-27. MECHANOSENSITIVE BRAIN TUMOR CELLS CONSTRUCT BLOOD-TUMOR BARRIER TO MASK CHEMOSENSITIVITY

Abstract Two major obstacles in brain cancer treatment are the blood-tumor barrier (BTB) and quiescent tumor cells. Here we show that Sox2+ cells directly project cellular processes to ensheathe capillaries medulloblastoma (MB), a process depends on mechanosensitive ion channel Piezo2. MB develops tissue stiffness gradient as function of distance capillaries. perceive substrate sustain local intracellular calcium, actomyosin tension, adhesion promote growth cell surface sequestration β-Catenin. Piezo2 knockout reverses WNT/β-Catenin signaling states between endothelial cells, compromises BTB, reduces quiescence markedly enhances response chemotherapy. Our study reveals construct BTB mask chemosensitivity. Targeting addresses properties underlie therapy failures cancer.