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.