Characterization of side population in thyroid cancer cell lines: Cancer stem-like cells are enriched partly but not exclusively

被引:193
作者
Mitsutake, Norisato [1 ]
Iwao, Atsuhiko
Nagai, Kazuhiro
Namba, Hiroyuki
Ohtsuru, Akira
Saenko, Vladimir
Yamashita, Shunichi
机构
[1] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Med, Atom Bomb Dis Inst, Nagasaki 8528523, Japan
[2] Nagasaki Univ, Grad Sch Biomed Sci, Dept Int Hlth & Radiat Res, Atom Bomb Dis Inst, Nagasaki 8528523, Japan
[3] Nagasaki Univ Hosp Med & Dent, Takashi Nagai Mem Int Hibakusha Med Ctr, Nagasaki 8528501, Japan
关键词
D O I
10.1210/en.2006-1553
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
There is increasing evidence that cancers contain their own stem-like cells called cancer stem cells ( CSCs). A small subset of cells, termed side population ( SP), has been identified using flow cytometric analysis. The SP cells have the ability to exclude the DNA binding dye, Hoechst33342, and are highly enriched for stem cells in many kinds of normal tissues. Because CSCs are thought to be drug resistant, SP cells in cancers might contain CSCs. We initially examined the presence of SP cells in several human thyroid cancer cell lines. A small percentage of SP cells were found in ARO ( 0.25%), FRO ( 0.1%), NPA ( 0.06%), and WRO ( 0.02%) cells but not TPC1 cells. After sorting, the SP cells generated both SP and non-SP cells in culture. The clonogenic ability of SP cells was significantly higher than that of non-SP cells. Moreover, the SP prevalence was dependent on cell density in culture, suggesting that SP cells preferentially survived at lower cell density. Microarray experiment revealed differential gene expression profile between SP and non-SP cells, and several genes related to stemness were up-regulated. However, non-SP population also contained cells that were tumorigenic in nude mice, and non-SP cells generated a small number of SP cells. These results suggest that cancer stem-like cells are partly, but not exclusively, enriched in SP population. Clarifying the key tumorigenic population might contribute to the establishment of a novel therapy for thyroid cancer.
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页码:1797 / 1803
页数:7
相关论文
共 28 条
[1]
Anaplastic thyroid carcinoma: Behavior, biology, and therapeutic approaches [J].
Ain, KB .
THYROID, 1998, 8 (08) :715-726
[2]
Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[3]
Androutsellis-Theotokis A, 2006, NATURE, V442, P823, DOI 10.1038/nature04940
[4]
Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[5]
Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties [J].
Chiba, Tetsuhiro ;
Kita, Kaoru ;
Zheng, Yun-Wen ;
Yokosuka, Osamu ;
Saisho, Hiromitsu ;
Iwama, Atsushi ;
Nakauchi, Hiromitsu ;
Taniguchi, Hideki .
HEPATOLOGY, 2006, 44 (01) :240-251
[6]
CYTO-TOXICITY, MUTAGENICITY AND DNA DAMAGE BY HOECHST-33342 [J].
DURAND, RE ;
OLIVE, PL .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1982, 30 (02) :111-116
[7]
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo [J].
Goodell, MA ;
Brose, K ;
Paradis, G ;
Conner, AS ;
Mulligan, RC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (04) :1797-1806
[8]
A distinct "side population" of cells with high drug efflux capacity in human tumor cells [J].
Hirschmann-Jax, C ;
Foster, AE ;
Wulf, GG ;
Nuchtern, JG ;
Jax, TW ;
Gobel, U ;
Goodell, MA ;
Brenner, MK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (39) :14228-14233
[9]
Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line [J].
Kondo, T ;
Setoguchi, T ;
Taga, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (03) :781-786
[10]
Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells [J].
Kubota, H ;
Avarbock, MR ;
Brinster, RL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (11) :6487-6492