Research News
Computerized Prostate Models Tumor Progression
Using a type of computer simulation known as cellular automata modeling, a research team led by David Basanta of the H. Lee Moffitt Cancer Center and Research Institute has created a computerized view of the human prostate gland that faithfully represents the interactions between early tumors and adjacent tissues. More importantly, this model generated hypotheses about tumor growth that were successfully tested in vivo. The investigators describe their model in the journal Cancer Research.
It is well-established that signaling interactions between the prostate gland and the surrounding stromal tissue, which includes smooth muscle, play an important role in the growth and spread of prostate cancer in humans. However, there is no clear picture of the role that these interactions play in tumor development, particularly the effect of transforming growth factor-β (TGF-β) on cancer progression.
In attempt to clarify this picture, Dr. Basanta and his colleagues created a hybrid cellular automata model that integrates five different types of cells with three different molecules thought to play an important signaling role between the prostate and neighboring stroma. They then used this model to probe the role that TGF-β plays in driving prostate cancer progression, and in particular, how TFG-β regulates the interactions between prostate tumor cells and the stroma.
Model runs, each of which encompassed approximately 55 years of real time cellular growth, showed that TGC-β production seems to have little effect on tumor growth, an unexpected finding. In contrast, the density of stromal cells surrounding nascent tumors had a significant impact on tumor progression, with prostates surrounded by a higher density of stromal cells being more resistant to takeover by a tumor than were prostates surrounded by a lower density of stromal cells. Only when metastasis has started does TGF-β begin to play a dominant role in tumor progression.
In fact, the model suggested that tumor cell production of TGF-β actually inhibits tumor progression by recruiting stromal cells to move toward the tumor. When the investigators then measured TGF-β levels in human prostate biopsies and examined them for evidence of stromal cell recruitment, they found that there was very little TGF-β in normal human prostate tissue compared to high levels of this growth factor in tumors along with increased biochemical activity by associated stromal cells.
This work, which was supported by the National Cancer Institute, is detailed in a paper titled, “The Role of Transforming Growth Factor-β-Mediated Tumor-Stroma Interactions in Prostate Cancer Progression: An Integrative Approach.” Investigators from Vanderbilt University, the Vanderbilt University Medical Center, and the Baylor College of Medicine also participated in this study. An abstract is available at the journal’s Web site.
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