Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers.
Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers.
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DOI：
10.1371/journal.pone.0010277
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发表时间：
2010-04-21
期刊：
影响因子：
3.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Deng S;Yang X;Lassus H;Liang S;Kaur S;Ye Q;Li C;Wang LP;Roby KF;Orsulic S;Connolly DC;Zhang Y;Montone K;Bützow R;Coukos G;Zhang L
乙醛脱氢酶同工型1（ALDH 1）已被证明可用于鉴定癌症干细胞。然而，我们对ALDH1在常见上皮癌及其相应正常组织中的表达和活性的了解仍然很大程度上缺乏。因此，我们的特点ALDH1表达在24种正常组织和大量的上皮肿瘤标本（6种癌症类型，n = 792）的免疫组化染色。 使用ALDEFUOR测定，还在16个原发性肿瘤标本和43个已建立的上皮癌细胞系中检测ALDH1活性。此外，分析了卵巢癌转基因小鼠模型和7种小鼠卵巢癌细胞系。我们发现ALDH 1在上皮癌中的表达水平和模式是显著不同的，并且它们与其相应的正常组织相关。ALDH1蛋白表达水平与通过ALDEFLUOR测定测量的ALDH1酶活性正相关。长期体外培养对上皮性肿瘤细胞ALDH 1活性无明显影响。与其他癌症的研究一致，我们发现ALDH1高表达与浆液性卵巢癌患者的不良临床结局显著相关（n = 439，p = 0.0036）。 最后，ALDHbr肿瘤细胞表现出癌症干细胞特性，并且对化疗具有抗性。作为一种新的肿瘤干细胞标志物，ALDH 1可用于其相应正常组织以相对有限或有限水平表达ALDH 1的肿瘤，如乳腺癌、肺癌、卵巢癌或结肠癌。
Aldehyde dehydrogenase isoform 1 (ALDH1) has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036). Finally, ALDHbr tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
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.
ALDH1A1 是恶性前列腺干细胞的标记物，也是前列腺癌患者预后的预测因子。
DOI：
10.1038/labinvest.2009.127
发表时间：
2010-02
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
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作者：
通讯作者：
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