"The beauty of our model is that it really represents the cancer cells very well," Quaranta said. "Sandy (Anderson) was able to capture the random behavior of cells."
In the model, when cells divide they randomly choose from a set of 100 different "phenotypes" ?behaviors that result from distinct genetic characteristics. For example, a cell might choose characteristics that allow it to divide more quickly or to detach from its neighbors. The investigators set the environmental conditions: these include the oxygen and nutrient concentrations and the landscape of connective tissue that surrounds the cells. They were surprised to find that the microenvironment around the tumor determines both the tumor's shape and its composition.
"What we get is a picture of cells that are evolving and growing within a microenvironment," Quaranta said. "The nice thing about computer simulations is you can create ‘what if' scenarios: what if we make the oxygen very high, what if we turn oxygen off in the middle of tumor growth, what if we change the landscape of connective tissue"
"By doing this we discovered new things that we didn't know before. And that is the hallmark of a good mathematical model: it's not just a repository of data that is put together; it actually tells you which variables are the important ones and gives outcomes that you wouldn't have otherwise predicted."
The current model predicts that in mild environmental conditions ?imagine a lush rainforest, Quaranta said ?many cell types co-exist and the tumor shape is round with smooth edges, characteristic of a non-invasive tumor. Under harsh environmental conditions ?imagine a desert ?the most aggressive cell types dominate and the tumor shape has fingering, invasive projections.
By changing a single condition ?oxygen concentration ?the investigators can modulate the tumor's degree of invasiveness, Quaranta said.
The findings suggest that current chemother
Source:Vanderbilt University Medical Center