26S proteasome activity is down-regulated in lung cancer stem-like cells propagated in vitro.
26S proteasome activity is down-regulated in lung cancer stem-like cells propagated in vitro.
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DOI：
10.1371/journal.pone.0013298
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发表时间：
2010-10-11
期刊：
影响因子：
3.7
通讯作者：
You M
中科院分区：
文献类型：
--
作者：
Pan J;Zhang Q;Wang Y;You M
癌症干细胞（CSC）是一小部分能够自我更新和维持肿瘤的癌细胞。消灭肿瘤干细胞是肿瘤起源和复发的根源，已成为提高肺癌生存率的一种有前途的方法。据报道，癌症干细胞存在于培养的肺癌细胞的侧群（SP）中。我们在这里报告的共存的一个独特的人口的非SP（NSP）的细胞，具有相当的自我更新能力相比，SP细胞在肺肿瘤球测定。与单层培养的相应细胞相比，由人非小细胞肺癌细胞系A549或H1299形成的肺肿瘤球显示出显著的形态学差异，并且干细胞标志物CD 133和OCT 3/4的表达增加。肺肿瘤球也表现出增加的致瘤潜力，因为在裸鼠中产生异种移植肿瘤仅需要10，000个肺肿瘤球细胞，而相同数量的单层细胞未能诱导肿瘤。我们还表明，肺肿瘤球显示降低26 S蛋白酶体活性相比，单层。通过在NSCLC细胞系中使用ZsGreen-cODC（指导鸟氨酸脱羧酶降解的C末端序列）报告基因测定，只有不到1%的单层培养物为ZsGreen阳性，表明26 S蛋白酶体较低，而肺肿瘤球体显示ZsGreen阳性细胞数量增加，表明球体培养物中CSC富集。
Cancer stem cells (CSCs) are a small subset of cancer cells capable of self-renewal and tumor maintenance. Eradicating cancer stem cells, the root of tumor origin and recurrence, has emerged as one promising approach to improve lung cancer survival. Cancer stem cells are reported to reside in the side population (SP) of cultured lung cancer cells. We report here the coexistence of a distinct population of non-SP (NSP) cells that have equivalent self-renewal capacity compared to SP cells in a lung tumor sphere assay. Compared with the corresponding cells in monolayer cultures, lung tumor spheres, formed from human non-small cell lung carcinoma cell lines A549 or H1299, showed marked morphologic differences and increased expression of the stem cell markers CD133 and OCT3/4. Lung tumor spheres also exhibited increased tumorigenic potential as only 10,000 lung tumor sphere cells were required to produce xenografts tumors in nude mice, whereas the same number of monolayer cells failed to induce tumors. We also demonstrate that lung tumor spheres showed decreased 26S proteasome activity compared to monolayer. By using the ZsGreen–cODC (C-terminal sequence that directs degradation of Ornithine Decarboxylase) reporter assay in NSCLC cell lines, only less than 1% monolayer cultures were ZsGreen positive indicating low 26S proteasome, whereas lung tumor sphere showed increased numbers of ZsGreen-positive cells, suggesting the enrichment of CSCs in sphere cultures.
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影响因子：
11.2
作者：
Harris MA;Yang H;Low BE;Mukherjee J;Guha A;Bronson RT;Shultz LD;Israel MA;Yun K
通讯作者：
Yun K
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
3.7
作者：
Levina V;Marrangoni AM;DeMarco R;Gorelik E;Lokshin AE
通讯作者：
Lokshin AE
影响因子：
3.5
作者：
Platet, Nadine;Mayol, Jean-Francois;Wion, Didier
通讯作者：
Wion, Didier