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Title: Manipulation of the nanoscale presentation of integrin ligand produces cancer cells with enhanced stemness and robust tumorigenicity
Authors: Wong, SHD 
Xu, X
Chen, X 
Xin, Y 
Xu, L
Lai, CHN
Oh, J
Wong, WKR
Wang, X
Han, S
You, W
Shuai, X
Wong, N
Tan, Y 
Duan, L
Bian, L
Issue Date: 14-Apr-2021
Source: Nano letters, 14 Apr. 2021, v. 21, no. 7, p. 3225-3236
Abstract: Developing strategies for efficient expansion of cancer stem-like cells (CSCs) in vitro will help investigate the mechanism underlying tumorigenesis and cancer recurrence. Herein, we report a dynamic culture substrate tethered with integrin ligand-bearing magnetic nanoparticles via a flexible polymeric linker to enable magnetic manipulation of the nanoscale ligand tether mobility. The cancer cells cultured on the substrate with high ligand tether mobility develop into large semispherical colonies with CSCs features, which can be abrogated by magnetically restricting the ligand tether mobility. Mechanistically, the substrate with high ligand tether mobility suppresses integrin-mediated mechanotransduction and histone-related methylation, thereby enhancing cancer cell stemness. The culture-derived high-stemness cells can generate tumors both locally and at the distant lung and uterus much more efficiently than the low-stemness cells. We believe that this magnetic nanoplatform provides a promising strategy for investigating the dynamic interaction between CSCs and the microenvironment and establishing a cost-effective tumor spheroid model.
Keywords: Cancer stem-like cells
Magnetic actuation
Nanoscale tether mobility
Tumor mechanobiology
Ligand presentation
Publisher: American Chemical Society
Journal: Nano letters 
ISSN: 1530-6984
EISSN: 1530-6992
DOI: 10.1021/acs.nanolett.1c00501
Rights: © 2021 American Chemical Society
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Nano Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
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