Label-free platform on pH-responsive chitosan: Adhesive heterogeneity for cancer stem-like cell isolation from A549 cells via integrin β4

• Published in: Carbohydrate polymers Vol. 239; p. 116168
• Main Authors: Yen, Chia-Hsiang, Li, Sheng-Tien, Cheng, Nai-Chen, Ji, You-Ren, Wang, Jyh-Horng, Young, Tai-Horng
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2020
• Subjects: A549 Cells; Animals; Cancer stem-like cell (CSLC); Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Adhesion; Cell adhesive strength; Cell Separation; Chitosan - chemistry; Female; Humans; Hydrogen-Ion Concentration; Integrin beta4 - metabolism; Integrin β4; Label-free isolation; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice; Mice, Nude; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Particle Size; pH-responsive chitosan; Surface Properties; Tumor Cells, Cultured; pH-responsive chitosan; Cancer stem-like cell (CSLC); Label-free isolation; Cell adhesive strength; Integrin β4
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.116168

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•The pH-dependent cell isolation on chitosan serves as a label-free platform.•In vitro studies proved; the isolated subpopulation exhibits superior cancer stem-like cell hallmarks.•In vivo xenografts showed strong tumorigenicity of the isolated subpopulation.•Integrin β4 is decisive in controlling cancer stem-like cell detachment of A549 cells.•The unique cell detachment ratio could be used for the evaluation of cancer prognosis.
Great efforts have been paid to develop methodologies for cancer stem-like cell (CSLC) isolation in anti-cancer research. The major obstacle lies in the lack of generic biomarkers for different cancer types and the requirement of complicated immuno-labeling procedures. The purpose of this study is to establish a label-free platform for CSLC isolation using pH-responsive chitosan. Based on the adhesive heterogeneity, 15.7 ± 1.9 % of human non-small cell lung cancer (NSCLC) cell line A549 detached from the chitosan substrate following medium pH elevation from 6.99 to 7.65 within 1 h. As a result, this subpopulation of cells with low adhesiveness exhibited superior CSLC hallmarks, including self-renewal, invasive and metastatic potential, therapeutic-resistance, colony formation in vitro, as well as nude mice xenograft in vivo for tumorigenesis, in comparison with their high-adhesive counterpart. Furthermore, integrin β4 is decisive in controlling CSLC detachment of NSCLC. Conclusively, this pH-dependent isolation provides new insights into biomaterial-based CSLC isolation.