title: Microfluidic Platform for Studying Chemotaxis of Adhesive Cells Revealed a Gradient-Dependent Migration and Acceleration of Cancer Stem Cells.
abstract: 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 under 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 real time. Our results showed the dynamic and differential response of both LCSC and dLCSC to chemotaxis, which was regulated by the β-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.
authors.affiliation: †Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.|‡Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institutes of City University of Hong Kong, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zou
authors.affiliation: †Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.|‡Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institutes of City University of Hong Kong, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Yue
authors.affiliation: †Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.
authors.forename: Wai-Kin
authors.initials: WK
authors.lastname: Yu
authors.affiliation: †Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: †Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.|‡Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institutes of City University of Hong Kong, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Chi-Chun
authors.initials: CC
authors.lastname: Fong
authors.affiliation: §State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: †Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People's Republic of China.|‡Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institutes of City University of Hong Kong, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Mengsu
authors.initials: M
authors.lastname: Yang
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D002633:Chemotaxis / Q000502:physiology*; D006801:Humans; D046210:Microfluidic Analytical Techniques; D008855:Microscopy, Electron, Scanning; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism