title: Reprogramming mediated radio-resistance of 3D-grown cancer cells.
abstract: In vitro 3D growth of tumors is a new cell culture model that more closely mimics the features of the in vivo environment and is being used increasingly in the field of biological and medical research. It has been demonstrated that cancer cells cultured in 3D matrices are more radio-resistant compared with cells in monolayers. However, the mechanisms causing this difference remain unclear. Here we show that cancer cells cultured in a 3D microenvironment demonstrated an increase in cells with stem cell properties. This was confirmed by the finding that cells in 3D cultures upregulated the gene and protein expression of the stem cell reprogramming factors such as OCT4, SOX2, NANOG, LIN28 and miR-302a, compared with cells in monolayers. Moreover, the expression of β-catenin, a regulating molecule of reprogramming factors, also increased in 3D-grown cancer cells. These findings suggest that cancer cells were reprogrammed to become stem cell-like cancer cells in a 3D growth culture microenvironment. Since cancer stem cell-like cells demonstrate an increased radio-resistance and chemo-resistance, our results offer a new perspective as to why. Our findings shed new light on understanding the features of the 3D growth cell model and its application in basic research into clinical radiotherapy and medicine.
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xue
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, 10032.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Grabham
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China hubr@impcas.ac.cn.
authors.forename: Burong
authors.initials: B
authors.lastname: Hu
mesh_terms: D002454:Cell Differentiation / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects*; D066330:Printing, Three-Dimensional; D011829:Radiation Dosage; D011836:Radiation Tolerance; D059016:Tumor Microenvironment / Q000528:radiation effects
keywords: 3D growth microenvironment; matrigel; radio-resistance; reprogramming; β-catenin