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Cancer stem cells made, not born
Date:8/18/2011

tem cells, in this new alternate model, more differentiated non-stem cells can revert to being stem-like cells. "That's not a hierarchical society at all," Lander said. "Cells aren't born into a medieval guild; they can change jobs."

Working with cancer cell lines cultured in the laboratory, scientists had observed that just as solid cancers tend towards certain proportions of cell states, cell lines in vitro also settled into a balance, or equilibrium. "We wanted to understand how cancer cells stably maintain characteristic proportions of these different states for extended periods of time," said Gupta. A better understanding of the mechanisms controlling that equilibrium could give a clearer picture of the nature of cancer at a cellular level.

To characterize how cancer maintains cellular equilibrium, the researchers studied two different breast cancer cell lines and examined three different cell states that were similar to normal breast epithelial cell types, known as basal, luminal, and stem-like.

The team sorted the different cell types from each other and then grew their relatively pure populations for six days. Remarkably, each of the three populations quickly returned to the same equilibrium and populations of non-stem cells generated new stem-like cells. "Even when you sort relatively pure populations, you quickly get back the same balance," said Lander.

The return to equilibrium proportions happens so rapidly that it cannot be due to different growth rates of the different cell types, but must instead be due to cells changing their state.

The authors showed that the process can be modeled and accurately predicted using a mathematical tool called a Markov model, in which cells change their states independently of one another. Although the process is completely decentralized, it quickly returns to the same equilibrium.

Surprisingly, the model predicted that non-stem cells can convert into stem-like
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Contact: Nicole Davis
ndavis@broadinstitute.org
Broad Institute of MIT and Harvard
Source:Eurekalert

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