Open AccessReprogramming mediated radio-resistance of 3D-grown cancer cells
Author(s) -
Guoqiang Xue,
Zhen Ren,
Peter Grabham,
Yaxiong Chen,
Jianwei Zhu,
Yarong Du,
Dong Pan,
Xiaoman Li,
Burong Hu
Publication year - 2015
Publication title -
journal of radiation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.643
H-Index - 60
eISSN - 1349-9157
pISSN - 0449-3060
DOI - 10.1093/jrr/rrv018
Subject(s) - sox2 , reprogramming , homeobox protein nanog , cancer stem cell , cancer cell , microbiology and biotechnology , lin28 , cancer research , stem cell , biology , cd44 , cancer , tumor microenvironment , cell culture , cell , embryonic stem cell , induced pluripotent stem cell , tumor cells , biochemistry , gene , genetics
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.