4.8 Article

Microfluidic Platform for Studying Chemotaxis of Adhesive Cells Revealed a Gradient-Dependent Migration and Acceleration of Cancer Stem Cells

期刊

ANALYTICAL CHEMISTRY
卷 87, 期 14, 页码 7098-7108

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.5b00873

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资金

  1. National Key Scientific Research Program (973 Program) [2012CB933302]
  2. Knowledge Innovation Program of Shenzhen Municiple Government [JCYJ20140419115507575]
  3. Research Grants Council of the Hong Kong Special Administrative Region, China (CRF) [CityU9/CRF/13G]
  4. State Key Laboratory of Environmental and Biological Analysis and Strategic Development Fund of HKBU [SKLP_14-15_P008]
  5. Guangdong Natural Science Foundation [2014A030310282]

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Recent studies reveal that solid tumors consist of heterogeneous cells with distinct phenotypes and functions. However, it is unclear how different subtypes of cancer cells migrate tinder chemotaxis. Here, we developed a microfluidic device capable of generating multiple stable gradients, culturing cells on-chip, and monitoring single cell. migratory behavior. The microfluidic platform was used to study gradient-induced chemotaxis of lung cancer Stem cell (LCSC) and differentiated LCSC (dLCSC) in teat time. Our :results showed the dynamic and differential response of both LCSC and dLCSC to chemotaxis, which Was regulated by the beta-catenin dependent Wnt signaling pathway. The Microfluidic analysis showed that LCSC and dLCSC from the same origin behaved differently in the same external stimuli, suggesting the importance of cancer cell heterogeneity. We also observed for the first time the acceleration of both LCSC and dLCSC during chemotaxis caused by increasing local concentration in different gradients, which could only be realized through the microfluidic approach. The Capability to analyze single cell chemotaxis under spatially controlled conditions provides a novel analytical platform for the study of cellular microenvironments and cancer cell metastasis.

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