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Researchers attack stem cells that cause colon cancer
Date:4/28/2010

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CSCs are a type of stem cell discovered less than 15 years ago and are believed to be the result of mutations of normal stem cells. When CSCs divide, they can develop into new CSCs or into any type of cancer cell. While CSCs make up only 1% of a tumor's cells, they are believed to play a pivotal role in the recurrence of tumors following chemotherapy.

Traditional chemotherapy is good at killing most tumor cells, but not CSCs. Cell studies have found that chemotherapy kills only some of the tumor's CSCs. As a result, tumors may shrink or even disappear with chemotherapy, but the CSCs survive, replicating themselves and eventually producing new tumor cells.

Given the crucial role they play in cancer, it is no surprise that research has focused on destroying the CSCs. But there is a problem: these cells are so similar to normal stem cells that eradicating CSCs may also eradicate normal stem cells, an unacceptable outcome.

Starving them out

"Because CSCs have properties similar to normal stem cells, we have to find a way to attack them while keeping the adult stem cells alive," Majumdar said. To do that, the research team inactivated a receptor that is found in increased amounts in colon cancer cells: the insulin-like growth factor receptor (IGF-1R). The colon cancer CSCs seem to need a fair amount of IGF to live, more than other cells, and they can't function without the IGF receptor.

"We found that cells that survive chemotherapy show high activation of the IGF receptor and other receptors," Majumdar said. "We thought if we could inhibit or lower the receptor, we may have a treatment strategy."

Working with human colon cancer cells, the researchers manipulated the cellular genetics using small interfering RNA (siRNA) to prevent the synthesis of IGF-1R. In this way, they reduced the number of IGF receptors by half, and reduced the number of CSCs by 35%.

Questions about toxicity remain
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Contact: Donna Krupa
media@faseb.org
714-765-2012
Federation of American Societies for Experimental Biology
Source:Eurekalert

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