Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells.
Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells.
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DOI：
10.1371/journal.pone.0042564
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Jiao J;Hindoyan A;Wang S;Tran LM;Goldstein AS;Lawson D;Chen D;Li Y;Guo C;Zhang B;Fazli L;Gleave M;Witte ON;Garraway IP;Wu H
晚期和抗去势前列腺癌(CRPC)的新疗法依赖于确定能够维持癌症净生长的细胞亚群的独特属性和途径。从小鼠前列腺中分离假定的干/祖细胞的最佳方案之一是LIN-；Sca1+；CD49fhi(LSchi)，它可以使体外球体形成活性增加10倍以上。我们以前已经证明，在Pten-空前列腺癌模型中，LSCHI亚群对于癌症的发生既是必要的，也是充分的。为了进一步改进这一浓缩方案，我们搜索了在去势小鼠前列腺后上调的细胞表面分子，并确定CD166为候选基因。CD166编码一种细胞表面分子，可进一步丰富WT LSchi和Pten Null LSchi的成球活性。重要的是，CD166可以在体外丰富良性原代人前列腺细胞的球体形成能力，并在体内诱导管状结构的形成。CD166在前列腺癌组织中表达上调，尤其是在前列腺癌组织中表达上调。虽然在Pten空前列腺癌模型中小鼠CD166的基因缺失不会干扰球体的形成或阻止前列腺癌的进展和CRPC的发展，但在前列腺癌干/祖细胞和抗去势亚群上的CD166的存在表明，它是一种具有靶向输送人类前列腺癌治疗药物的细胞表面分子。
New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin-;Sca1+;CD49fhi (LSChi), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSChi subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSChi and Pten null LSChi. Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics.
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纯化和直接转化上皮祖细胞从原代人前列腺中。
影响因子：
14.8
作者：
通讯作者：
--
DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Chao MP;Alizadeh AA;Tang C;Jan M;Weissman-Tsukamoto R;Zhao F;Park CY;Weissman IL;Majeti R
通讯作者：
Majeti R
影响因子：
2.8
作者：
Garraway, Isla P.;Sun, Wenyi;Tran, Chau P.;Perner, Sven;Zhang, Bao;Goldstein, Andrew S.;Hahm, Scott A.;Haider, Maahum;Head, Christian S.;Reiter, Robert E.;Rubin, Mark A.;Witte, Owen N.
通讯作者：
Witte, Owen N.