Cancer Stem Cells

ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets†‡§

  1. Yuchun Luo1,
  2. Katiuscia Dallaglio1,2,
  3. Ying Chen3,
  4. William A. Robinson4,
  5. Steven E. Robinson4,
  6. Martin D. McCarter5,
  7. Jianbin Wang6,
  8. Rene Gonzalez4,
  9. David C. Thompson7,
  10. David A. Norris1,8,
  11. Dennis R. Roop1,2,
  12. Vasilis Vasiliou3,
  13. Mayumi Fujita1,2,8,¶,*

Article first published online: 20 SEP 2012

DOI: 10.1002/stem.1193

Issue

STEM CELLS

STEM CELLS

Volume 30, Issue 10, pages 2100–2113, October 2012

Additional Information

How to Cite

Luo, Y., Dallaglio, K., Chen, Y., Robinson, W. A., Robinson, S. E., McCarter, M. D., Wang, J., Gonzalez, R., Thompson, D. C., Norris, D. A., Roop, D. R., Vasiliou, V. and Fujita, M. (2012), ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets. STEM CELLS, 30: 2100–2113. doi: 10.1002/stem.1193

Author Information

  1. 1

    Department of Dermatology, University of Colorado Denver, Aurora, Colorado, USA

  2. 2

    Charles C Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Denver, Aurora, Colorado, USA

  3. 3

    Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, USA

  4. 4

    Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA

  5. 5

    Department of Surgery, University of Colorado Denver, Aurora, Colorado, USA

  6. 6

    Department of Biochemistry and Molecular Genetics, and

  7. 7

    Clinical Pharmacy, University of Colorado Denver, Aurora, Colorado, USA

  8. 8

    Denver Veterans Affairs Medical Center, Denver, Colorado, USA

  1. Telephone: 303-724-4045; Fax: 303-724-4048

*Department of Dermatology, University of Colorado Denver, Mail Stop 8127, 12801 E. 17th Ave., Rm 4124, Aurora, Colorado 80045, USA

  1. †

    Author contributions: Y.L.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; K.D., Y.C., and J.W.: collection and assembly of data, data analysis and interpretation, and final approval of manuscript; W.A.R., S.E.R., M.D.M., and R.G.: provision of study material or patients and final approval of manuscript; D.C.T., D.A.N., D.R.R., and V.V.: data analysis and interpretation and final approval of manuscript; M.F.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS August 7, 2012.

  4. Telephone: 303-724-4045; Fax: 303-724-4048

Publication History

  1. Issue published online: 20 SEP 2012
  2. Article first published online: 20 SEP 2012
  3. Accepted manuscript online: 7 AUG 2012 09:00AM EST
  4. Manuscript Accepted: 26 JUN 2012
  5. Manuscript Received: 28 FEB 2012

Funded by

  • NIH. Grant Number: CA125833
  • Veterans Affairs Merit Review Award
  • UCCC
  • Wendy Will Case Cancer Fund
  • Tadamitsu Cancer Research Fund
  • NEI. Grant Numbers: EY17963, EY11490

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Additional Supporting Information may be found in the online version of this article.

FilenameFormatSizeDescription
sc-12-0203_sm_SupplFigure1.pdf168KFigure S1. Expression of ALDH isoforms in human melanoma cell lines. The copy number of human ALDH1A1 (1A1) and ALDH1A3 (1A3) was analyzed by qRT-PCR. mRNAs of ALDH+ and ALDH- subpopulations obtained from human melanoma cell lines (1205Lu, A375, WM239A and HS294T) were analyzed. Copy number was counted and determined by standard curve analysis.
sc-12-0203_sm_SupplFigure2.pdf168KFigure S2. Representative flow cytometric analysis of GFP-expressing cells. ALDH+1205Lu cells were transfected with GFP-shRNA control plasmid (sh-ctrl) or GFP-shRNA-ALDH1A3 plasmid (sh-1A3). GFP-positive (representing successful transfection) and DAPI-negative (representing live cells) cells were sorted for in vivo tumorigenesis study in Fig. 3H.
sc-12-0203_sm_SupplFigure3.pdf168KFigure S3. Supervised hierarchical clustering of 1,196 differentially expressed transcripts between ALDH+ and ALDH- cells from xenografted patient melanomas (MF347, MB929 and MB947m). Colored spots indicate upregulated (red) or downregulated (blue) genes.
sc-12-0203_sm_SupplFigure4.pdf168KFigure S4. qRT-PCR analysis of ADAR, CDC42 and USH1C in 1205Lu cells. (A) Expression of mRNAs in ALDH7plus; and ALDH− subpopulation of 1205Lu cells. (B) Expression of mRNAs after knockdown of ALDH1A3 (si-1A3) in ALDH+1205Lu cells. Expression levels were normalized to GAPDH. Data represent mean ± SEM (n=3). *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared with transfection of control siRNA (si-ctrl).
sc-12-0203_sm_SupplMaterials.pdf313KSupplemental Data
sc-12-0203_sm_SupplTable1.pdf168KSupplemental Table 1.
sc-12-0203_sm_SupplTable2.pdf168KSupplemental Table 2.
sc-12-0203_sm_SupplTable3.pdf168KSupplemental Table 3.

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