Breast Cancer Cells Exposed to Vibration Increase NK Cell-Mediated Killing Efficiency

초록

Breast Cancer (BC), a type of solid tumor, has immunosuppressive mechanisms that limit the cytotoxic capacity of immune effector cells such as Natural Killer (NK) cells, unlike hematologic tumors [1-2]. However, BC located relatively further away from the body, such as those in breast, facilitates the transmission of vibrational stimuli more effectively compared to cancers in other tissues. As a therapeutic strategy for BC, the goal is to enhance NK cell-mediated killing acti efficiency by applying vibrations to BC cells. We identified upregulation of NKG2D ligands, such as MICA/B and ULBP1-3, in BC cells exposed to vibration, indicating that effective NKG2D/NKG2DL binding was induced between NK cells and BC cells. It is recognized that applying vibration to BC cells increases stiffness [3], and promotes the release of perforin and granzyme B from NK cells [4]. Additionally, Piezo1, a major mechanosensitive channel expressed in NK cells, regulates NK functions especially in solid tumors [4]. We observed upregulation of perforin, granzyme B, and Piezo1 expression in NK cells co-cultured with BC cells exposed to vibration using RT-PCR. As a result, NK cell-mediated cytotoxicity was significantly higher for BC cells exposed to vibration than the control. It was verified through lactate dehydrogenase (LDH) cytotoxicity assay and live/dead assay.