The gene, known as RhoGDI2, is missing or present in low levels in invasive, metastatic cancer, says a study by University of Virginia researchers in today's issue of Cancer Research. This finding could lead to new tests to help doctors determine the best way to treat individual cancers, and eventually could lead to gene therapy to treat aggressive forms of cancer.
"We found a gene that, when lost in human cancer cells, may indicate that the cancer has the potential to metastasize," says study author Dr. Dan Theodorescu, a professor of urology and molecular physiology at the University of Virginia Health System in Charlottesville.
To isolate the gene responsible for metastasis, Theodorescu and his team compared two types of bladder cancer -- one aggressive and invasive, the other a localized, non-spreading cancer. They found the aggressive form of cancer expressed low levels of RhoGDI2.
Cancer can develop only when the body's functions go awry. Normally, human cells grow to replace old, dying cells. If new cells form when the body doesn't need them and older cells don't die off, a tumor develops from all those extra cells. Some tumors are benign and generally don't cause problems. Others are malignant; these tumors can invade and damage other cells and travel to other parts of the body via the bloodstream.
For that whole process to occur, however, numerous genes have to be altered or destroyed. According to the researchers, replacing even the function of one of those damaged genes may stop the process that lets tumors spread.
That's exactly what happened in lab experiments with RhoGDI2. The researchers injected 15 mice with an aggressive form of bladder cancer. Eight of the mice also received injections of RhoGDI2. All of the mice that didn't receive the gene therapy had metastatic cancer, with an average of 32 tumors per mouse. Only four of the mice that received RhoGDI2 treatment had any metastasis, and those that did had an average of five lung tumors.
The researchers also examined 105 tumors from prostate, lung, breast, colorectal, gastroesophageal, kidney, liver, ovarian and pancreatic cancers to see if they would find reduced levels of RhoGDI2 in these cancers, and they did.
Theodorescu says it could be possible to develop a test to look for levels of RhoGDI2 in tumors, which would let doctors treat their patients more accurately and effectively. For example, someone with low levels of RhoGDI2 might be a good candidate for chemotherapy, since it is likely the tumor will be more aggressive. After more research, it might be possible to replace RhoGDI2 in cancer patients so their cancer doesn't metastasize, he says.
Dr. Duane Superneau, chief of medical genetics at the Ochsner Clinic Foundation in New Orleans, says this is an exciting study.
"This gene appears to be important in the metastasis of cancer," says Superneau. He adds this knowledge could offer new strategies for treatment, and it could act as a marker for the early detection of aggressive cancer. He points out this gene doesn't appear to affect tumor growth, but the tumor wouldn't spread. That means cancer patients would still need to have surgery to have the tumor removed, but might not need chemotherapy afterwards because the cancer cells won't have spread to other sites in the body.
Theodorescu and his colleagues are studying RhoGDI2 to see if they can learn how it controls metastasis, because, he says, if they know how it works, they may be able to manipulate it and develop new treatments for cancer patients.
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