Primary tumor genotype is an important determinant in identification of lung cancer propagating cells.
Primary tumor genotype is an important determinant in identification of lung cancer propagating cells.
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DOI：
10.1016/j.stem.2010.05.021
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发表时间：
2010-07-02
期刊：
影响因子：
23.9
通讯作者：
Kim CF
中科院分区：
文献类型：
--
作者：
Curtis SJ;Sinkevicius KW;Li D;Lau AN;Roach RR;Zamponi R;Woolfenden AE;Kirsch DG;Wong KK;Kim CF
成功的癌症治疗需要消除或使所有能够再生肿瘤的肿瘤细胞丧失能力。因此，治疗进展需要表征能够在体内增殖肿瘤的细胞。我们发现了肿瘤基因型和肿瘤增殖细胞（TPC）分离之间的重要联系。最常见的人类肺癌的三种小鼠模型各自具有具有独特细胞表面表型的TPC。细胞表面标志物Sca 1不会富集致癌Kras启动的肿瘤中的TPC，并且只有Sca 1阴性细胞繁殖EGFR突变肿瘤。相反，Sca 1阳性细胞在p53缺陷的Kras肿瘤中富集肿瘤增殖活性。因此，仅在一个基因座处基因型不同的原发性肿瘤可以具有带有不同标记物的肿瘤增殖细胞群。我们的研究表明，在研究中必须考虑肿瘤样本的基因型，以识别、表征和靶向肿瘤增殖细胞。根据三种易处理的肺腺癌小鼠模型中肿瘤起始的遗传事件，表面标记Sca 1在识别具有肿瘤增殖活性的细胞方面具有不同的成功率。这些发现揭示了肿瘤基因型对肿瘤增殖细胞表型的影响，这可能具有重要的治疗意义。- 识别第一个肺肿瘤繁殖细胞群-不同基因型的肺癌具有带有不同标记物的肿瘤繁殖细胞-肿瘤样本应按基因型分离以研究肿瘤繁殖细胞
Successful cancer therapy requires the elimination or incapacitation of all tumor cells capable of regenerating a tumor. Therapeutic advances therefore necessitate the characterization of the cells that are able to propagate a tumor in vivo. We show an important link between tumor genotype and isolation of tumor-propagating cells (TPCs). Three mouse models of the most common form of human lung cancer each had TPCs with a unique cell surface phenotype. The cell surface marker Sca1 did not enrich for TPCs in tumors initiated with oncogenic Kras, and only Sca1-negative cells propagated EGFR mutant tumors. In contrast, Sca1-positive cells were enriched for tumor-propagating activity in Kras tumors with p53 deficiency. Primary tumors that differ in genotype at just one locus can therefore have tumor-propagating cell populations with distinct markers. Our studies show that the genotype of tumor samples must be considered in studies to identify, characterize, and target tumor-propagating cells. Depending on the tumor initiating genetic event in three tractable mouse models of lung adenocarcinoma, the surface maker Sca1 had variable success in identifying cells with tumor-propagating activity. These findings uncover the impact that tumor genotype can have on the phenotype of tumor-propagating cells, which may have important therapeutic significance. -identification of the first lung tumor-propagating cell population -lung cancers of different genotype have tumor-propagating cells with distinct markers -tumor samples should be separated by genotype to study tumor-propagating cells
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影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
DOI：
10.1634/stemcells.2008-0838
发表时间：
2009-03
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Teisanu RM;Lagasse E;Whitesides JF;Stripp BR
通讯作者：
Stripp BR
影响因子：
5.2
作者：
Cho, Robert W.;Wang, Xinhao;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
5.2
作者：
McQualter, Jonathan L.;Brouard, Nathalie;Bertoncello, Ivan
通讯作者：
Bertoncello, Ivan