Format

Send to

Choose Destination
See comment in PubMed Commons below
Nature. 2015 Sep 10;525(7568):261-4. doi: 10.1038/nature14971. Epub 2015 Aug 26.

A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity.

Author information

1
School of Physics and Astronomy, University of Edinburgh, JCMB, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK.
2
Program for Evolutionary Dynamics, Harvard University, One Brattle Square, Cambridge, Massachusetts 02138, USA.
3
Department of Mathematics, Harvard University, One Oxford Street, Cambridge, Massachusetts 02138, USA.
4
The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, 401 North Broadway, Weinberg 2242, Baltimore, Maryland 21231, USA.
5
Ludwig Center and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, Maryland 21287, USA.
6
Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, Massachusetts 02138, USA.

Abstract

Most cancers in humans are large, measuring centimetres in diameter, and composed of many billions of cells. An equivalent mass of normal cells would be highly heterogeneous as a result of the mutations that occur during each cell division. What is remarkable about cancers is that virtually every neoplastic cell within a large tumour often contains the same core set of genetic alterations, with heterogeneity confined to mutations that emerge late during tumour growth. How such alterations expand within the spatially constrained three-dimensional architecture of a tumour, and come to dominate a large, pre-existing lesion, has been unclear. Here we describe a model for tumour evolution that shows how short-range dispersal and cell turnover can account for rapid cell mixing inside the tumour. We show that even a small selective advantage of a single cell within a large tumour allows the descendants of that cell to replace the precursor mass in a clinically relevant time frame. We also demonstrate that the same mechanisms can be responsible for the rapid onset of resistance to chemotherapy. Our model not only provides insights into spatial and temporal aspects of tumour growth, but also suggests that targeting short-range cellular migratory activity could have marked effects on tumour growth rates.

Comment in

PMID:
26308893
PMCID:
PMC4782800
DOI:
10.1038/nature14971
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center