April 5, 2012

Stem Cells Hold Clues for Colon Cancer

(Ivanhoe Newswire) -- A new study provides insight into where colon cancer may come from and possible therapeutic targets for the disease.

A team of researchers are using a clinically engineered mouse model for colorectal cancer. Investigators can now use the mouse to better understand how and where colorectal cancer comes from.

Colorectal cancer is the second leading cause of cancer deaths in the United States. These tumors are thought to arise from a series of mutations in intestinal stem cells, which are long-lived, self-renewing cells that give rise to all cell types in the intestinal tract.

For more than 30 years, scientists believed that intestinal stem cells were mostly quiescent, proliferating only rarely in order to protect the tissue against cancer. However, in 2007, researchers reported finding a population of intestinal stem cells (marked by the molecule Lgr5) that were highly proliferative.

Those findings "really changed the way we think about intestinal stem cells," Robert Coffey, Jr., M.D., Ingram Professor of Cancer Research, co-chair of Vanderbilt's Epithelial Biology Center and senior author on the study, was quoted as saying.

"It came to so dominate the field that it raised the question about whether quiescent stem cells even exist“¦and that's where we enter into the picture."

Coffey and his team study the epidermal growth factor (EGF) signaling pathway — which includes a family of receptors known as ErbBs — and its role in cancers of epithelial tissues, like the intestinal tract.

Researcher Anne Powell, Ph.D., led the recent experiments showing that Lrig1, a molecule that regulates ErbB activity, is present in intestinal cells that have 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 was quoted as saying.

"We also show that they're distinct from the Lgr5-expressing stem cells that had become a sort of 'hallmark' stem cell population“¦with different gene expression profiles and different proliferative status."

The team also showed that Lrig1 is not only a marker of intestinal stem cells, but also acts as a tumor suppressor and prevents the growth and proliferative signals of the ErbB family.

Fellow colleague 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 discovery downgrades the importance of ErbB signaling in the behavior of intestinal stem cells from which colorectal cancer may arise.

"Most exciting 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", Coffey was quoted as saying

SOURCE: Cell, March 29, 2012