Cell softness regulates tumorigenicity and stemness of cancer cells

Identifying and sorting highly tumorigenic and metastatic tumor cells from a heterogeneous cell population is a daunting challenge. Here, we show that microfluidic devices can be used to sort marker-based heterogeneous cancer stem cells (CSC) into mechanically stiff and soft subpopulations. The isolated soft tumor cells (< 400 Pa) but not the stiff ones (> 700 Pa) can form a tumor in immunocompetent mice with 100 cells per inoculation. Notably, only the soft, but not the stiff cells, isolated from CD133(+), ALDH(+), or side population CSCs, are able to form a tumor with only 100 cells in NOD-SCID or immunocompetent mice. The Wnt signaling protein BCL9L is upregulated in soft tumor cells and regulates their stemness and tumorigenicity. Clinically, BCL9L expression is correlated with a worse prognosis. Our findings suggest that the intrinsic softness is a unique marker of highly tumorigenic and metastatic tumor cells.

Automated summary

Microfluidic devices can sort cancer stem cells into mechanically stiff and soft subpopulations, with soft tumor cells showing higher tumorigenicity. The upregulation of Wnt signaling protein BCL9L in soft tumor cells is associated with their stemness and tumorigenicity. These findings suggest that intrinsic softness can serve as a unique marker for highly tumorigenic and metastatic tumor cells.