New Discovery.

New discovery may lead to novel treatments for a variety of cancers sify news

2010-10-28 17:20:00 ======================================================

Scientists have discovered that the overproduction of a key protein in stem cells causes those stem cells to form cancerous tumors. Their work may lead to new treatments for a variety of cancers.

Dr. Jon Horowitz, associate professor of molecular biomedical sciences, and a team of at North Carolina State University researchers looked at the protein SP2, which regulates the activity of other genes.

They knew that elevated amounts of SP2 had been observed in human prostate-cancer patients, and that these levels only increased as the tumors became more dangerous.

Horowitz and the team decided to look at SP2 as a possible cause of tumor formation in epithelial cell-derived tumors, which comprise about 80 percent of all human tumors; epithelial cells cover the body's internal and external surfaces.

They found that overproduction of the SP2 protein in epithelial stem cells stopped them from spawning mature descendants. The affected stem cells, unable to produce mature cells, just kept proliferating, resulting in the formation of tumors.

"Something happens to normal stem cells that changes the way SP2 is regulated, and it starts being overproduced," Horowitz said.

"SP2 basically hijacks the stem cell, and turns it into its evil twin - a cancer cell," he said.

Now that the link between tumor formation and SP2 has been shown, Horowitz says, scientists can turn their attention to looking at ways to target the overproduction of this protein.

The researchers' results are published in the Nov. 3 edition of the journal Cancer Research. (ANI)
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Cancer's hiding spots revealed

Contact: Jen Hirsch
jfhirsch@mit.edu
617-253-1682
Massachusetts Institute of Technology 

Discovery that tumor cells can escape from chemotherapy could lead to new treatments that prevent relapse

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CAMBRIDGE, Mass. -- In a study of mice with lymphoma, MIT biologists have discovered that a small number of cancer cells escape chemotherapy by hiding out in the thymus, an organ where immune cells mature. Within the thymus, the cancer cells are bathed in growth factors that protect them from the drugs' effects. Those cells are likely the source of relapsed tumors, said Michael Hemann, MIT assistant professor of biology, who led the study.

The researchers plan to soon begin tests, in mice, of drugs that interfere with one of those protective factors. Those drugs were originally developed to treat arthritis, and are now in clinical trials for that use. Such a drug, used in combination with traditional chemotherapy, could offer a one-two punch that eliminates residual tumor cells and prevents cancer relapse, according to the researchers.

"Successful cancer therapy needs to involve a component that kills tumor cells as well as a component that blocks pro-survival signals," said Hemann, who is a member of MIT's David H. Koch Institute for Integrative Cancer Research. "Current cancer therapies fail to target this survival response."

Hemann and graduate student Luke Gilbert described the findings in the Oct. 29 issue of the journal Cell.

In the new study, the researchers treated mice with lymphoma with doxorubicin, a drug commonly used to treat a wide range of cancers, including blood cancers. They found that during treatment, cells that line the blood vessels release cytokines ? small proteins that influence immune responses and cell development.

The exact mechanism is not known, but the researchers believe that chemotherapy-induced DNA damage provokes those blood-vessel cells to launch a stress response that is normally intended to protect progenitor cells ? immature cells that can become different types of blood cells. That stress response includes the release of cytokines such as interleukin-6, which promotes cell survival.

"In response to environmental stress, the hardwired response is to protect privileged cells in that area, i.e., progenitor cells," said Hemann. "These pathways are being coopted by tumor cells, in response to the frontline cancer therapies that we use."

The discovery marks the first time scientists have seen a protective signal evoked by chemotherapy in the area surrounding the tumor, known as the tumor microenvironment. "It's completely unexpected that drugs would promote a survival response," said Hemann. "The impact of local survival factors is generally not considered when administering chemotherapy, let alone the idea that frontline chemotherapy would induce pro-survival signals."

It remains to be seen if the results will translate to human patients, but the finding does suggest several potential drug targets, including IL-6 and a protein called Bcl2, which is activated by IL-6 and signals cells to stay alive. While the MIT researchers observed this protective effect only in the thymus, they believe there may be other protected areas where tumor cells hide, such as the bone marrow.

This finding could help explain why tumors that have spread to other parts of the body before detection are more resistant to frontline chemotherapy: They may have already engaged a protective cytokine system, helping them to survive the drugs' effects.

Hemann hopes to further clarify the mechanism in future studies, in collaboration with Professor Michael Yaffe, also a member of the Koch Institute. He also plans to investigate whether this kind of pro-survival signal is elicited in other types of cancer, including tumors that have metastasized.

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