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PMID: 19706777 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The role of transforming growth factor-beta-mediated tumor-stroma interactions in prostate cancer progression: an integrative approach.

Cancer research ·Vol. 69 ·No. 17 ·2009-09-01 ·Pages 7111-20

Basanta D, Strand DW, Lukner RB, Franco OE, Cliffel DE, Ayala GE, Hayward SW, Anderson AR

Abstract

We have implemented a hybrid cellular automata model based on the structure of human prostate that recapitulates key interactions in nascent tumor foci between tumor cells and adjacent stroma. Model simulations show how stochastic interactions between tumor cells and stroma may lead to a structural suppression of tumor growth, modest proliferation, or unopposed tumor growth. The model incorporates key aspects of prostate tumor progression, including transforming growth factor-beta (TGF-beta), matrix-degrading enzyme activity, and stromal activation. It also examines the importance of TGF-beta during tumor progression and the role of stromal cell density in regulating tumor growth. The validity of one of the key predictions of the model about the effect of epithelial TGF-beta production on glandular stability was tested in vivo. These experimental results confirmed the ability of the model to generate testable biological predictions in addition to providing new avenues of experimental interest. This work underscores the need for more pathologically representative models to cooperatively drive computational and biological modeling, which together could eventually lead to more accurate diagnoses and treatments of prostate cancer.

MeSH Terms
Animals Cell Adhesion Cell Communication Cell Movement Cell Proliferation Disease Progression Humans Male Mice Models, Biological Prostate/pathology Prostatic Neoplasms/metabolism,pathology Stromal Cells/pathology Transforming Growth Factor beta/metabolism
Chemicals
Transforming Growth Factor beta
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Basanta David
Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. [email protected]
Strand Douglas W
Lukner Ralf B
Franco Omar E
Cliffel David E
Ayala Gustavo E
Hayward Simon W
Anderson Alexander R A
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Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-08-3957
Email
[email protected]
Published
2009-09-01
Epub
2009-00-25
Pages
7111-20
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC2748342
Subset
IM
Grants
NCI NIH HHS · U54 CA126568 · United States
NCI NIH HHS · U54 CA113007 · United States
NCI NIH HHS · 1U54 CA126505 · United States
NCI NIH HHS · 5U54 CA113007 · United States
NCI NIH HHS · U54 CA126505 · United States
NCI NIH HHS · T32 CA009592 · United States
NCI NIH HHS · U54 CA126505-030002 · United States
NCI NIH HHS · 1U54 CA 126568 · United States
NCI NIH HHS · 2T32 CA009592-21A1 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-08-3957 PMC Full Text View journal details
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