Jiadi Lv1, Yaoping Liu2, Feiran Cheng1, Jiping Li3, Yabo Zhou1, Tianzhen Zhang1, Nannan Zhou1, Cong Li1, Zhenfeng Wang1, Longfei Ma1, Mengyu Liu1, Qiang Zhu1, Xiaohan Liu1, Ke Tang4, Jingwei Ma4, Huafeng Zhang4, Jing Xie1, Yi Fang5, Haizeng Zhang5, Ning Wang6, Yuying Liu1,7, Bo Huang1,4,7. 1. Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China. 2. Institute of Microelectronics, Peking University, Beijing, China. 3. Beijing Smartchip Microelectronics Technology Company Limited, Beijing, China. 4. Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China. 5. National Cancer Center/Cancer Hospital, CAMS, Beijing, China. 6. Deaprtment of Mechanical Science and Technology, The Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. 7. Clinical Immunology Center, CAMS, Beijing, China.
Abstract
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.
Identifying and sorting highly tumorigenic and metastatic span>n class="Disease">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.
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