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通过醛脱氢酶活性检测分离的前列腺癌细胞干细胞的基因表达谱。

Gene expression profiles of prostate cancer stem cells isolated by aldehyde dehydrogenase activity assay.

机构信息

Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

J Urol. 2012 Jul;188(1):294-9. doi: 10.1016/j.juro.2012.02.2555. Epub 2012 May 16.

DOI:10.1016/j.juro.2012.02.2555
PMID:22608744
Abstract

PURPOSE

Prostate cancer cells include a small population of cancer stem-like/cancer initiating cells, which have roles in cancer initiation and progression. Recently aldehyde dehydrogenase activity was used to isolate stem cells of various cancer and normal cells. We evaluated the aldehyde dehydrogenase activity of the human prostate cancer cell line 22Rv1 (ATCC®) with the ALDEFLUOR® assay and determined its potency as prostate cancer stem-like/cancer initiating cells.

MATERIALS AND METHODS

The human prostate cancer cell line 22Rv1 was labeled with ALDEFLUOR reagent and analyzed by flow cytometry. ALDH1(high) and ALDH1(low) cells were isolated and tumorigenicity was evaluated by xenograft transplantation into NOD/SCID mice. Tumor sphere forming ability was evaluated by culturing in a floating condition. Invasion capability was evaluated by the Matrigel™ invasion assay. Gene expression profiling was assessed by microarrays and reverse transcriptase-polymerase chain reaction.

RESULTS

ALDH1(high) cells were detected in 6.8% of 22Rv1 cells, which showed significantly higher tumorigenicity than ALDH1(low) cells in NOD/SCID mice (p < 0.05). Gene expression profiling revealed higher expression of the stem cell related genes PROM1 and NKX3-1 in ALDH1(high) cells than in ALDH1(low) cells. ALDH1(high) cells also showed higher invasive capability and sphere forming capability than ALDH1(low) cells.

CONCLUSIONS

Results indicate that cancer stem-like/cancer initiating cells are enriched in the ALDH1(high) population of the prostate cancer cell line 22Rv1. This approach may provide a breakthrough to further clarify prostate cancer stem-like/cancer initiating cells. To our knowledge this is the first report of cancer stem-like/cancer initiating cells of 22Rv1 using the aldehyde dehydrogenase activity assay.

摘要

目的

前列腺癌细胞中包含一小部分癌症干细胞样/癌症起始细胞,它们在癌症的发生和发展中起作用。最近,醛脱氢酶活性被用于分离各种癌症和正常细胞的干细胞。我们使用 ALDEFLUOR®检测法评估了人前列腺癌细胞系 22Rv1(ATCC®)的醛脱氢酶活性,并确定其作为前列腺癌干细胞样/癌症起始细胞的能力。

材料和方法

用人前列腺癌细胞系 22Rv1 标记 ALDEFLUOR 试剂,并用流式细胞术进行分析。分离 ALDH1(高)和 ALDH1(低)细胞,并通过异种移植到 NOD/SCID 小鼠中评估其致瘤性。通过在悬浮条件下培养评估肿瘤球形成能力。通过 Matrigel™侵袭测定评估侵袭能力。通过微阵列和逆转录聚合酶链反应评估基因表达谱。

结果

在 22Rv1 细胞中检测到 6.8%的 ALDH1(高)细胞,其在 NOD/SCID 小鼠中的致瘤性明显高于 ALDH1(低)细胞(p<0.05)。基因表达谱分析显示,ALDH1(高)细胞中与干细胞相关的基因 PROM1 和 NKX3-1 的表达明显高于 ALDH1(低)细胞。ALDH1(高)细胞还表现出比 ALDH1(低)细胞更高的侵袭能力和球体形成能力。

结论

结果表明,前列腺癌细胞系 22Rv1 中的癌症干细胞样/癌症起始细胞在 ALDH1(高)群体中富集。这种方法可能为进一步阐明前列腺癌干细胞样/癌症起始细胞提供突破。据我们所知,这是首次使用醛脱氢酶活性测定法报告 22Rv1 的癌症干细胞样/癌症起始细胞。

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