Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15034-9. doi: 10.1073/pnas.0802211105. Epub 2008 Sep 24.

Preneoplastic lesion growth driven by the death of adjacent normal stem cells.

Author information

1
Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. dchao@fhcrc.org

Abstract

Clonal expansion of premalignant lesions is an important step in the progression to cancer. This process is commonly considered to be a consequence of sustaining a proliferative mutation. Here, we investigate whether the growth trajectory of clones can be better described by a model in which clone growth does not depend on a proliferative advantage. We developed a simple computer model of clonal expansion in an epithelium in which mutant clones can only colonize space left unoccupied by the death of adjacent normal stem cells. In this model, competition for space occurs along the frontier between mutant and normal territories, and both the shapes and the growth rates of lesions are governed by the differences between mutant and normal cells' replication or apoptosis rates. The behavior of this model of clonal expansion along a mutant clone's frontier, when apoptosis of both normal and mutant cells is included, matches the growth of UVB-induced p53-mutant clones in mouse dorsal epidermis better than a standard exponential growth model that does not include tissue architecture. The model predicts precancer cell mutation and death rates that agree with biological observations. These results support the hypothesis that clonal expansion of premalignant lesions can be driven by agents, such as ionizing or nonionizing radiation, that cause cell killing but do not directly stimulate cell replication.

PMID:
18815380
PMCID:
PMC2567488
DOI:
10.1073/pnas.0802211105
[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 HighWire Icon for PubMed Central
    Loading ...
    Support Center