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

Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces

View ORCID ProfileJacob G. Scott, View ORCID ProfileAndrew Dhawan, View ORCID ProfileAnita Hjelmeland, View ORCID ProfileJustin Lathia, Anastasia Chumakova, View ORCID ProfileMasahiro Hitomi, View ORCID ProfileAlexander G. Fletcher, Philip K. Maini, View ORCID ProfileAlexander R. A. Anderson
doi: https://doi.org/10.1101/169615
Jacob G. Scott
aDepartments of Translational Hematology and Oncology Research and Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA
bWolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jacob G. Scott
Andrew Dhawan
aDepartments of Translational Hematology and Oncology Research and Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA
cDepartment of Oncology, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew Dhawan
Anita Hjelmeland
dDepartment of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, AL, US
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anita Hjelmeland
Justin Lathia
eDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Justin Lathia
Anastasia Chumakova
eDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masahiro Hitomi
aDepartments of Translational Hematology and Oncology Research and Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA
eDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Masahiro Hitomi
Alexander G. Fletcher
fSchool of Mathematics and Statistics, University of Sheffield, Sheffield, UK
gBateson Centre, University of Sheffield, Sheffield, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexander G. Fletcher
Philip K. Maini
bWolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander R. A. Anderson
hDepartment of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexander R. A. Anderson
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Since the first evidence for cancer stem cells in leukemia, experimentalists have sought to identify tumorigenic subpopulations in solid tumors. In parallel, scientists have argued over the implications of the existence of this subpopulation. On one side, the cancer stem cell hypothesis posits that a small subset of cells within a tumor are responsible for tumorigenesis and are capable of recapitulating the entire tumor on their own. Under this hypothesis, a tumor may be conceptualized as a series of coupled compartments, representing populations of progressively differentiated cell types, starting from stem cells. The allure of this model is that it elegantly explains our therapeutic failures: we have been targeting the wrong cells. Alternatively, the stochastic model states that all cells in a tumor can have stem-like properties, and have an equally small capability of forming a tumor. As tumors are, by nature, heterogeneous, there is ample evidence to support both hypotheses. We propose a mechanistic mathematical description that integrates these two theories, settling the dissonance between the schools of thought and providing a road map for integrating disparate experimental results into a single theoretical framework. We present experimental results from clonogenic assays that demonstrate the importance of defining this novel formulation, and the clarity that is provided when interpreting these results through the lens of this formulation.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted August 14, 2017.
Download PDF
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.
Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces
(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
Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces
Jacob G. Scott, Andrew Dhawan, Anita Hjelmeland, Justin Lathia, Anastasia Chumakova, Masahiro Hitomi, Alexander G. Fletcher, Philip K. Maini, Alexander R. A. Anderson
bioRxiv 169615; doi: https://doi.org/10.1101/169615
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces
Jacob G. Scott, Andrew Dhawan, Anita Hjelmeland, Justin Lathia, Anastasia Chumakova, Masahiro Hitomi, Alexander G. Fletcher, Philip K. Maini, Alexander R. A. Anderson
bioRxiv 169615; doi: https://doi.org/10.1101/169615

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 (3514)
  • Biochemistry (7367)
  • Bioengineering (5346)
  • Bioinformatics (20324)
  • Biophysics (10045)
  • Cancer Biology (7776)
  • Cell Biology (11352)
  • Clinical Trials (138)
  • Developmental Biology (6453)
  • Ecology (9980)
  • Epidemiology (2065)
  • Evolutionary Biology (13356)
  • Genetics (9373)
  • Genomics (12612)
  • Immunology (7725)
  • Microbiology (19103)
  • Molecular Biology (7465)
  • Neuroscience (41153)
  • Paleontology (301)
  • Pathology (1235)
  • Pharmacology and Toxicology (2142)
  • Physiology (3178)
  • Plant Biology (6880)
  • Scientific Communication and Education (1276)
  • Synthetic Biology (1900)
  • Systems Biology (5328)
  • Zoology (1091)