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


CONCLUSIONS
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.
Baker
Stuart G
SG
Biometry Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, USA. sb16i@nih.gov
Soto
Ana M
AM
Sonnenschein
Carlos
C
Cappuccio
Antonio
A
Potter
John D
JD
Kramer
Barnett S
BS
D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D016764:Cell Polarity; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008962:Models, Theoretical; D009024:Morphogenesis; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*