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Label-free platform on pH-responsive chitosan: Adhesive heterogeneity for cancer stem-like cell isolation from A549
Chia-Hsiang Yen1, Sheng-Tien Li1, Nai-Chen Cheng2
1Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd., Taipei, Taiwan.
Abstract:
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.
