Gene Expression Profiles of Prostate Cancer Stem Cells Isolated by Aldehyde Dehydrogenase Activity Assay

• Published in: The Journal of urology Vol. 188; no. 1; pp. 294 - 299
• Main Authors: Nishida, Sachiyo, Hirohashi, Yoshihiko, Torigoe, Toshihiko, Kitamura, Hiroshi, Takahashi, Akari, Masumori, Naoya, Tsukamoto, Taiji, Sato, Noriyuki
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2012; Elsevier
• Subjects: aldehyde dehydrogenase; Animals; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; carcinoma; Cell Line, Tumor; Flow Cytometry; gene expression; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Isoenzymes - biosynthesis; Isoenzymes - genetics; Male; Male genital diseases; Medical sciences; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasms, Experimental; neoplastic stem cells; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nephrology. Urinary tract diseases; prostate; Prostate - enzymology; Prostate - pathology; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Retinal Dehydrogenase - biosynthesis; Retinal Dehydrogenase - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - genetics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; aldehyde dehydrogenase; Dulbecco's modified Eagle's medium; reverse transcriptase-PCR; diethylaminobenzaldehyde; ALDH; DMEM; CSC; carcinoma; neoplastic stem cells; RT-PCR; cancer stem-like cell; prostate; glyceraldehyde-3-phosphate dehydrogenase; CIC; cancer initiating cell; DEAB; GAPDH; gene expression; PCR; polymerase chain reaction; Nephrology; Urinary system disease; Carcinoma; Prostate disease; Enzyme; Stem cell; ); Malignant tumor; Gene expression; Urology; Gene expression profile; Enzymatic activity; Aldehyde dehydrogenase (NAD; Isolated cell; Oxidoreductases; Urogenital system; Male genital diseases; Prostate cancer; Prostate; Tumor cell; Cancer
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1016/j.juro.2012.02.2555

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. ALDH1high and ALDH1low 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 ALDH1high cells were detected in 6.8% of 22Rv1 cells, which showed significantly higher tumorigenicity than ALDH1low 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 ALDH1high cells than in ALDH1low cells. ALDH1high cells also showed higher invasive capability and sphere forming capability than ALDH1low cells. Conclusions Results indicate that cancer stem-like/cancer initiating cells are enriched in the ALDH1high 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.