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Open Access Highly Accessed Research article

Plausibility of stromal initiation of epithelial cancers without a mutation in the epithelium: a computer simulation of morphostats

Stuart G Baker1*, Ana M Soto2, Carlos Sonnenschein2, Antonio Cappuccio3, John D Potter4 and Barnett S Kramer5

Author Affiliations

1 Biometry Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, USA

2 Department of Anatomy and Cell Biology, Tufts University School of Medicine, Boston, USA

3 Bioinformatics and Computational Systems Biology of Cancer, Institut Curie, Paris, France

4 Division of Public Health Sciences, Fred Hutchinson Cancer Research, Seattle, USA

5 Office of Disease Prevention, National Institutes of Health, Bethesda, USA

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BMC Cancer 2009, 9:89  doi:10.1186/1471-2407-9-89

Published: 23 March 2009

Abstract

Background

There is experimental evidence from animal models favoring the notion that the disruption of interactions between stroma and epithelium plays an important role in the initiation of carcinogenesis. These disrupted interactions are hypothesized to be mediated by molecules, termed morphostats, which diffuse through the tissue to determine cell phenotype and maintain tissue architecture.

Methods

We developed a computer simulation based on simple properties of cell renewal and morphostats.

Results

Under the computer simulation, the disruption of the morphostat gradient in the stroma generated epithelial precursors of cancer without any mutation in the epithelium.

Conclusion

The model is consistent with the possibility that the accumulation of genetic and epigenetic changes found in tumors could arise after the formation of a founder population of aberrant cells, defined as cells that are created by low or insufficient morphostat levels and that no longer respond to morphostat concentrations. Because the model is biologically plausible, we hope that these results will stimulate further experiments.