Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

Ielizaveta Gorodetska, Anne Offermann, Jakob Püschel, Vasyl Lukiyanchuk, Diana Gaete, Anastasia Kurzyukova, Vera Labitzky, Franziska Schwarz, Tobias Lange, Franziska Knopf, View ORCID ProfileBen Wielockx, Mechthild Krause, Sven Perner, Anna Dubrovska
doi: https://doi.org/10.1101/2021.05.08.443223
Ielizaveta Gorodetska
1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne Offermann
2Institute of Pathology, University Hospital Schleswig-Holstein, Luebeck, Germany; Pathology, Research Center, Borstel, Leibniz Lung Center, Borstel, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jakob Püschel
1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vasyl Lukiyanchuk
1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diana Gaete
3Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anastasia Kurzyukova
4Technische Universität Dresden, CRTD - Center for Regenerative Therapies TU Dresden, Center for Healthy Aging, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vera Labitzky
5Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, Hamburg, University Medical Center Hamburg-Eppendorf, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Franziska Schwarz
1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
8Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
9German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tobias Lange
5Institute of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Cancer Center, Hamburg, University Medical Center Hamburg-Eppendorf, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Franziska Knopf
4Technische Universität Dresden, CRTD - Center for Regenerative Therapies TU Dresden, Center for Healthy Aging, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ben Wielockx
3Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ben Wielockx
Mechthild Krause
1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
6Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
7National Center for Tumor Diseases (NCT), partner site Dresden: German Cancer Research Center (DKFZ), Heidelberg; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
8Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
9German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sven Perner
2Institute of Pathology, University Hospital Schleswig-Holstein, Luebeck, Germany; Pathology, Research Center, Borstel, Leibniz Lung Center, Borstel, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: anna.dubrovska@oncoray.de
Anna Dubrovska
1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
7National Center for Tumor Diseases (NCT), partner site Dresden: German Cancer Research Center (DKFZ), Heidelberg; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
8Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, Dresden, Germany
9German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: anna.dubrovska@oncoray.de
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Cancer stem cells (CSC) are characterized by high self-renewal capacity, tumor-initiating potential, and therapy resistance. Aldehyde dehydrogenase (ALDH)+ cell population serves as an indicator of prostate CSCs with increased therapy resistance, enhanced DNA double-strand break repair, and activated epithelial-mesenchymal transition (EMT) and migration. Numerous ALDH genes contribute to ALDH enzymatic activity; however, only some of them showed clinical relevance. We found that ALDH1A1 and ALDH1A3 genes functionally regulate CSC properties and radiation sensitivity of PCa. We revealed a negative correlation between ALDH1A1 and ALDH1A3 expression in publicly available prostate cancer (PCa) datasets and demonstrated that ALDH1A1 and ALDH1A3 have opposing predictive value for biochemical recurrence-free survival. Our data suggest an association of ALDH1A1 with the metastatic burden, elucidating the role of ALDH genes in the metastatic spread and homing to the bone, which can be, at least partially, attributed to regulating the transforming growth factor beta 1 (TGFB1) and matrix metalloproteinases (MMPs). ALDH genes play a diverse role in PCa development under AR and β-catenin-dependent regulation, with ALDH1A1 becoming dominant in later stages of tumor development when PCa cells gain androgen independence. Taken together, our results indicate that ALDH1A1 and ALDH1A3 modulate PCa radiosensitivity, regulate CSCs phenotype, and spread of PCa cells to the bone, therefore having clinical implication for identifying patients at high risk for progression to metastatic disease.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    ALDH
    aldehyde dehydrogenase
    AR
    androgen receptor
    BAAA
    bodipy-aminoacetaldehyde
    BAA
    bodipy-aminoacetate
    BM
    bone metastatic
    CSC
    cancer stem cell
    DEAB
    diethylaminobenzaldehyde
    DHT
    dihydrotestosterone
    DMEM
    Dulbecco’s Modified Eagles Medium
    DMSO
    dimethyl sulfoxide
    DoC
    duct of Cuvier
    dpf
    days post fertilization
    DTT
    dithiothreitol
    ECM
    extracellular matrix
    EGF
    epidermal growth factor
    EMT
    epithelial-mesenchymal transition
    Enza
    Enzalutamide
    FBS
    fetal bovine serum
    FFPE
    fresh frozen paraffin embedded
    FGF
    fibroblast growth factor
    FITC
    fluorescein isothiocyanate
    FSC
    forward scatter
    gDNA
    genomic DNA
    i.c.
    intracardiac
    IHC
    immunohistochemistry
    iPSA
    initial prostate-specific antigen levels
    LN
    lymph node
    LM
    lung metastatic
    Luc
    luciferase
    mCRPC
    metastatic castration resistant prostate cancer
    MMP
    matrix metalloprotease
    NSG
    NOD scid gamma mouse
    P
    parental
    PBS
    phosphate-buffered saline
    PCa
    prostate cancer
    PE
    plating efficacy
    PFA
    paraformaldehyde
    PI
    propidium iodide
    PT
    primary tumor
    RPMI
    Roswell Park Memorial Institute Medium
    RR
    radioresistant
    RT
    room temperature
    RT
    radiation therapy
    -RT
    sample without added reverse transcriptase enzyme
    SF
    surviving fraction
    shNA
    non-silencing small hairpin RNA
    shRNA
    small hairpin RNA
    siRNA
    small interfering RNA
    siSCR
    scrambled small interfering RNA
    SPSS
    Statistical Package for the Social Sciences
    SSC
    side scatter
    SUMO
    Statistical Utility for Microarray and Omics data software
    TCGA
    The Cancer Genome Atlas
    TMA
    tissue microarray
    TNM
    tumor, nodus и metastasis
    WF
    wide field
    Zol
    zoledronic acid
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
    Back to top
    PreviousNext
    Posted May 10, 2021.
    Download PDF

    Supplementary Material

    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases
    Ielizaveta Gorodetska, Anne Offermann, Jakob Püschel, Vasyl Lukiyanchuk, Diana Gaete, Anastasia Kurzyukova, Vera Labitzky, Franziska Schwarz, Tobias Lange, Franziska Knopf, Ben Wielockx, Mechthild Krause, Sven Perner, Anna Dubrovska
    bioRxiv 2021.05.08.443223; doi: https://doi.org/10.1101/2021.05.08.443223
    Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
    Citation Tools
    The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases
    Ielizaveta Gorodetska, Anne Offermann, Jakob Püschel, Vasyl Lukiyanchuk, Diana Gaete, Anastasia Kurzyukova, Vera Labitzky, Franziska Schwarz, Tobias Lange, Franziska Knopf, Ben Wielockx, Mechthild Krause, Sven Perner, Anna Dubrovska
    bioRxiv 2021.05.08.443223; doi: https://doi.org/10.1101/2021.05.08.443223

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Cancer Biology
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (3479)
    • Biochemistry (7318)
    • Bioengineering (5296)
    • Bioinformatics (20197)
    • Biophysics (9976)
    • Cancer Biology (7703)
    • Cell Biology (11250)
    • Clinical Trials (138)
    • Developmental Biology (6417)
    • Ecology (9916)
    • Epidemiology (2065)
    • Evolutionary Biology (13280)
    • Genetics (9352)
    • Genomics (12554)
    • Immunology (7674)
    • Microbiology (18939)
    • Molecular Biology (7417)
    • Neuroscience (40891)
    • Paleontology (298)
    • Pathology (1226)
    • Pharmacology and Toxicology (2126)
    • Physiology (3140)
    • Plant Biology (6838)
    • Scientific Communication and Education (1270)
    • Synthetic Biology (1891)
    • Systems Biology (5296)
    • Zoology (1085)