BREAST CANCER CELL DECISION-MAKING REGULATED BY CALCIUM-RELATED TRPM7 ION CHANNEL

brest cancer cells;microchannel;calcium;Chemical & Biomolecular Engineering

Zhu, Tian

Johns Hopkins University

关键词: brest cancer cells;    microchannel;    calcium;    Chemical & Biomolecular Engineering;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60154/ZHU-THESIS-2018.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Approximately 90% of all cancer-related deaths arise from the metastatic spread of primary tumours. Cell migration plays a critical role in the metastatic process. Steering migration in cancer metastasis through chemotactic stimulus has been wildly studied, yet it remains unclear how cell collects environmental cues and makes a decision at an intersection. In a confined microenvironment, cells move preferentially to the lower hydraulic resistance channel. To decipher the coupling parameters, we fabricated customized PDMS based microfluidic devices with trifurcated microchannels for cell to make decision. We found cells utilized cortical actins to counteract the hydraulic resistance in the microchannel and cells lose ability to sense or follow the low hydraulic resistance path without myosin IIA. Additionally, the stretching of the membrane by the hydraulic resistance induced the opening of TRPM7 ion channel controlling calcium. The calcium enrichment close to the membrane enhanced cytoskeleton remodeling. Unraveling the mechanisms for cell migration in 3D confinement may prompt new approaches to develop cancer diagnostics and therapies.