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Newly identified stem cells may hold clues to colon cancer
Date:3/29/2012

nts showing that Lrig1, a molecule that regulates ErbB activity, is present in intestinal cells that have the qualities of stem cells (self-renewal, and the ability to produce all the cells of the intestine).

"Essentially, what we show is that the Lrig1-expressing cells are stem cells and they are largely quiescent," Powell said. "We also show that they're distinct from the Lgr5-expressing stem cells that had become a sort of 'hallmark' stem cell populationwith different gene expression profiles and different proliferative status."

They also showed that Lrig1 is not only a marker of intestinal stem cells, but also acts as a tumor suppressor and inhibits the growth and proliferative signals of the ErbB family acting as a sort of "brake" on cell proliferation that can lead to cancer.

Postdoctoral fellow Yang Wang, Ph.D., eliminated Lrig1 in mice and showed that nearly all of those mice developed intestinal tumors, providing further evidence suggesting that Lrig1 functions as a tumor suppressor.

The findings underscore the importance of ErbB signaling in the behavior of intestinal stem cells from which colorectal cancer may arise.

Most exciting, said Coffey, is that the mouse model his lab has generated as a part of these studies is one of the only mouse models to develop tumors in section of the intestines where most human tumors develop: the colon. One additional advantage of this model, in contrast to others, is that the tumors develop quickly and can be easily monitored with endoscopy, which will make it easier to assess how therapeutic interventions are working.

"We are fairly confident that this will be the 'go-to' model to study colon cancer in mice for the foreseeable future," Coffey said.


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Contact: Melissa Marino
melissa.marino@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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