The identification of stem-cell-like cancer cells through conventional methods that depend on stem cell markers is often unreliable. We developed a mechanical method for selecting tumorigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.
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We would like to thank J. Winer for help with fibrin-gel protocols. This work was supported by funds from Huazhong University of Science and Technology (HUST), the National Basic Research Program of China (2012CB932500) (B.H.), the China Natural National Science Foundation (30911120482) (B.H.), the Fundamental Research Funds for the Central Universities (HUST-2011TS027) (B.H.), and USA NIH grant GM072744 (N.W.).
The authors declare no competing financial interests.
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Liu, J., Tan, Y., Zhang, H. et al. Soft fibrin gels promote selection and growth of tumorigenic cells. Nature Mater 11, 734–741 (2012). https://doi.org/10.1038/nmat3361
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