A facile method for generating tumorigenic cancer stem cell spheroids from diverse cancer cell lines

Although cancer stem cells (CSCs) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of patient-derived diverse CSCs. Here, we developed a functional polymer thin film (PTF) platform that promotes conversion of human cancer cell lines to highly tumorigenic spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular spheroids within 24 hours, with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed an enormous increase in the expression of CSC-associated genes and acquired dramatically increased drug resistance compared with monolayer-cultured controls. These spheroids also showed greatly enhanced xenograft tumor-forming ability and metastasis capacity in nude mice. By enabling the generation of tumorigenic spheroids as a patient-derived CSC substitute, the surface platform described here will likely contribute to CSC-related basic research and drug development. Overall design: mRNA profiles of 8 day-SKOV3-ssiCSC spheroids and 2D-cultured SKOV3 control were generated by deep sequencing, in duplicate, using Hiseq-2500.

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Choi M, Yu SJ, Choi Y, Lee HR, Lee E, Lee E, Lee Y, Song J, Son JG, Lee TG, Kim JY, Kang S, Baek J, Lee D, Im SG, Jon S