Microfluidic Platform for Investigating Osteocyte Mechanoregulation of Breast Cancer Bone Metastasis

Abstract

Bone metastasis is a severe complication that occurs in approximately 85% of patients with advanced breast cancer. Although the potential of exercise in attenuating metastatic tumor growth in bone had been shown in vivo, the role of mechanical loading on bone in preventing bone metastasis remains unknown. Osteocytes, as the major mechanosensory bone cells, are identified regulators in mediating loading inhibited bone metastasis in vitro. However, there is no ideal platform currently available for investigating the impact and mechanism underlying loading reduced bone metastasis. To bridge the gap between in vivo and in vitro experiments, this thesis develops a novel microfluidic cancer extravasation platform that integrates bone mechanical loading and real-time bi-directional signaling between multiple cell populations within the bone metastasis environment. Using our microfluidic extravasation platform, we observed the overall effect that mechanically-stimulated osteocytes regulate breast cancer transendothelial extravasation indeed, and the specific impact is breast cancer type dependent.M.A.S

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