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Cancer Res ; 78(24): 6890-6902, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30352813

RESUMO

: Although cancer stem cells (CSC) 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 diverse, patient-derived CSC. Here, we present a functional polymer thin film (PTF) platform that promotes conversion of cancer cells to highly tumorigenic three-dimensional (3D) 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 tumor spheroids within 24 hours with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed a significant increase in the expression of CSC-associated genes and acquired increased drug resistance compared with two-dimensional monolayer-cultured controls. These spheroids also exhibited enhanced xenograft tumor-forming ability and metastatic capacity in nude mice. By enabling the generation of tumorigenic spheroids from diverse cancer cells, the surface platform described here harbors the potential to contribute to CSC-related basic research and drug development. SIGNIFICANCE: A new cell culture technology enables highly tumorigenic 3D spheroids to be easily generated from various cancer cell sources in the common laboratory.


Assuntos
Células-Tronco Neoplásicas/citologia , Polímeros/química , Esferoides Celulares/citologia , Animais , Carcinogênese/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Feminino , Genoma , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Reprodutibilidade dos Testes
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