U.Va. team identifies gene that could halt spread of cancer

CHARLOTTESVILLE, Va., Nov. 14 – A gene may be responsible for halting the spread of cancer through the body, according to scientists at the University of Virginia Health System. The gene, called RhoGDI2, could also be used as a warning to help catch the spread of cancer in patients earlier. A multidisciplinary team of scientists, led by Dr. Dan Theodorescu, professor of urology and molecular physiology at U.Va., used advanced DNA technology to discover that low levels of RhoGDI2 were found more often in invasive cancer than in localized cancer. Their findings are published in the Nov. 15 issue of Cancer Research. This is the first study linking the RhoGDI2 gene to cancer metastasis.

"We found the greatest RhoGDI2 loss in invasive and metastatic cancer tissue. At this point, it is clear the gene plays a role in the cancer's lethal progression to metastasis and not in the initial formation of the cancer, " Theodorescu said. "As such, it is one of only a handful of true metastasis suppressor genes known."

To identify RhoGDI2 as a metastasis suppressor gene, the U.Va. researchers "replaced" missing RhoGDI2 genes in human metastatic cancer cells that did not manufacture the gene on their own. "We replaced the gene in the most aggressive cell lines we had in the lab," Theodorescu said. "The first thing we noticed was that the cells grew normally. We were initially disappointed until we discovered that cells with the RhoGDI2 replaced had lost the ability to metastasize."

When the RhoGDI2 gene is active in a cancer cell, Theodorescu explained, the cell produces a protein that prevents the cancer cell from invading other organs. U.Va. scientists believe a future diagnostic test for low levels of this protein could be developed. The absence of the protein could serve as a red flag for physicians and help determine which cancers have the propensity to spread. Used in combination with other prognostic tests and biomarkers, RhoGDI2 expression may help determine the most effective and least invasive treatment for each patient based on the seriousness of the cancer.

If the gene can be "awakened" in metastatic cancers using gene therapy or other approaches, Theodorescu's research could offer new therapeutic options to treat metastatic disease since once cancer metastasizes, or spreads, to other organs it is much less curable. In ongoing research, Theodorescu hopes to discover exactly how the RhoGDI2 gene regulates cell metastasis.

Scientists at U.Va. and The Genomics Institute of the Novartis Research Foundation contributing to the study were: J. J. Gildea, M. J. Seraj, G. Oxford, M. A. Harding, G. M. Hampton, C. A. Moskaluk, H. F. Frierson and M. R. Conaway. Their research was supported by the National Cancer Institute and the American Cancer Society.

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