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Scientific ReportsVolume 6, 9 March 2016, Article number 22828

Selective advantage of trisomic human cells cultured in non-standard conditions(Article)(Open Access)

  • Rutledge, S.D.,
  • Douglas, T.A.,
  • Nicholson, J.M.,
  • Vila-Casadesús, M.,
  • Kantzler, C.L.,
  • Wangsa, D.,
  • Barroso-Vilares, M.,
  • Kale, S.D.,
  • Logarinho, E.,
  • Cimini, D.
  • View Correspondence (jump link)
  • aDepartment of Biological Sciences, Blacksburg, VA 24061, United States
  • bBiocomplexity Institute, Virginia Tech, 1015 Life Sciences Circle, Blacksburg, VA 24061, United States
  • cBiomedical Engineering, Virginia Tech, Blacksburg, VA 24061, United States
  • dBioinformatics Platform, CIBERehd, Barcelona, Spain
  • eGenetics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, United States
  • fAging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto, Rua Alfredo Allen 208, Porto, 4200-135, Portugal
  • gCell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, Porto, 4200-319, Portugal

Abstract

An abnormal chromosome number, a condition known as aneuploidy, is a ubiquitous feature of cancer cells. A number of studies have shown that aneuploidy impairs cellular fitness. However, there is also evidence that aneuploidy can arise in response to specific challenges and can confer a selective advantage under certain environmental stresses. Cancer cells are likely exposed to a number of challenging conditions arising within the tumor microenvironment. To investigate whether aneuploidy may confer a selective advantage to cancer cells, we employed a controlled experimental system. We used the diploid, colorectal cancer cell line DLD1 and two DLD1-derived cell lines carrying single-chromosome aneuploidies to assess a number of cancer cell properties. Such properties, which included rates of proliferation and apoptosis, anchorage-independent growth, and invasiveness, were assessed both under standard culture conditions and under conditions of stress (i.e., serum starvation, drug treatment, hypoxia). Similar experiments were performed in diploid vs. aneuploid non-transformed human primary cells. Overall, our data show that aneuploidy can confer selective advantage to human cells cultured under non-standard conditions. These findings indicate that aneuploidy can increase the adaptability of cells, even those, such as cancer cells, that are already characterized by increased proliferative capacity and aggressive tumorigenic phenotypes.

Indexed keywords

EMTREE medical terms:cell culturecell proliferationepithelium cellhumanphysiologytrisomy
MeSH:Cell ProliferationCells, CulturedEpithelial CellsHumansTrisomy

Funding details

Funding sponsor Funding number Acronym
Virginia Polytechnic Institute and State University
National Science Foundation
See opportunities		MCB-1517506,MCB-0842551
Horowitz Foundation for Social PolicyRGY0069/2010

  • 1

    We would like to acknowledge Thomas Ried (National Cancer Institute, NIH) for providing the aneuploid CRC cell lines. We also thank Silke Hauf and Rich Walker for providing important feedback throughout the execution of this project. Finally, we thank all the members of the Hauf and Cimini labs for helpful comments and discussions. SDR was partly supported through Graduate Teaching Assistantships provided by the Dept. of Biological Sciences (Virginia Tech). Work in the Cimini lab partly funded by NSF grants MCB-0842551 and MCB-1517506 and HFSP grant RGY0069/2010. We further acknowledge the Virginia Tech University Libraries for covering the publication fees through the Open Access Subvention Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • ISSN: 20452322
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1038/srep22828
  • PubMed ID: 26956415
  • Document Type: Article
  • Publisher: Nature Publishing Group

  Cimini, D.; Department of Biological Sciences, Blacksburg, VA, United States;
© Copyright 2016 Elsevier B.V., All rights reserved.

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