Cancer requires support from immune system to develop, UT Southwestern research... (gene and one mutated gene develop the di...)

Cancer requires support from immune system to develop, UT Southwestern researchers report

Date:10/30/2008

gene and one mutated gene develop the disease.

The UT Southwestern researchers had previously found in mice that plexiform neurofibromas develop from Schwann cells that have two mutated copies of Nf1. In addition, they discovered that even before a plexiform neurofibroma begins to form around a nerve, mast cells migrate into the area.

In the current study, the scientists used genetically engineered mice to confirm first that the animals need two mutated copies of Nf1 in their Schwann cells to develop neurofibromas, which the rest of their cells can still have one normal and one mutant Nf1 gene.

In addition, a bone marrow transplant from normal mice with two normal Nf1 genes prevented 90 percent of the engineered mice from developing neurofibromas, confirming that even with two mutated genes in the Schwann cells, a mutated copy must also be present in other cells. Bone marrow is the source of mast cells, blood cells and many other types of cells that circulate through blood vessels.

The researchers then focused on the role of mast cells in tumor formation, particularly a molecule on the cells' surface called c-kit, which controls many functions, including migration and proliferation.

The mice engineered to develop tumors were given the drug imatinib mesylate, also known as Gleevec. The drug, known to inhibit c-kit, currently is used to treat chronic myelogenous leukemia and other cancers.

Positron emission tomography scans showed that Gleevec halved the metabolic activity of the tumors, while later examination confirmed that the tumors were much smaller than in placebo-treated mice.

"We found there was a requirement from the immune system to interact with the tumor for the tumor to grow," Dr. Parada said. "When mast cells are blocked, the tumor cannot grow."

During the course of these experiments, the researchers learned about a girl who had a large neurofibroma that could not be removed s
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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