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.

中文翻译：

---

细胞柔软度调节癌细胞的致瘤性和干性


从异质细胞群中识别和分选高致瘤性和转移性肿瘤细胞是一项艰巨的挑战。在这里，我们展示了微流体装置可用于将基于标记的异质癌症干细胞（CSC）分类为机械刚性和柔软的亚群。每次接种 100 个细胞的免疫活性小鼠中，分离的软肿瘤细胞 (< 400 Pa) 可形成肿瘤，而硬肿瘤细胞 (> 700 Pa) 则不能。值得注意的是，在 NOD-SCID 或免疫功能正常的小鼠中，只有从 CD133 ⁺ 、ALDH ⁺或侧群 CSC 中分离出的软细胞能够形成只有 100 个细胞的肿瘤，而硬细胞则不然。 Wnt 信号蛋白 BCL9L 在软肿瘤细胞中上调，并调节其干细胞性和致瘤性。临床上，BCL9L 表达与较差的预后相关。我们的研究结果表明，内在的柔软度是高致瘤性和转移性肿瘤细胞的独特标志。