TY - JOUR
T1 - Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells
AU - Debeb, Bisrat G.
AU - Zhang, Xiaomei
AU - Krishnamurthy, Savitri
AU - Gao, Hui
AU - Cohen, Evan
AU - Li, Li
AU - Rodriguez, Angel Augusto
AU - Landis, Melissa D.
AU - Lucci, Anthony
AU - Ueno, Naoto T.
AU - Robertson, Fredika
AU - Xu, Wei
AU - Lacerda, Lara
AU - Buchholz, Thomas A.
AU - Cristofanilli, Massimo
AU - Reuben, James M.
AU - Lewis, Michael T.
AU - Woodward, Wendy A.
N1 - Funding Information:
The National Institute of Health R01CA138239-01;The State of Texas Grant for Rare and Aggressive Cancers; The American Airlines Komen Foundation Promise Grant KGO81287; The University of Texas M.D. Anderson Cancer Center Institutional Research Grant; The University of Texas Health Sciences Center KL2 RR024149.
PY - 2010/7/8
Y1 - 2010/7/8
N2 - Background: Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells.Results: 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including β-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres.Conclusions: 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.
AB - Background: Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells.Results: 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including β-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres.Conclusions: 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.
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U2 - 10.1186/1476-4598-9-180
DO - 10.1186/1476-4598-9-180
M3 - Article
C2 - 20615238
AN - SCOPUS:77955506627
SN - 1476-4598
VL - 9
JO - Molecular Cancer
JF - Molecular Cancer
M1 - 180
ER -