UNC researchers identify virus gene involved in tumor cell growth, spread

04/15/04

CHAPEL HILL -- In studying a virus that causes the skin cancer Kaposi's sarcoma, University of North Carolina at Chapel Hill scientists have identified a viral gene that switches on cellular genes involved in promoting tumor cell growth and metastasis throughout the body.

The K1 gene in Kaposi's sarcoma-associated herpesvirus (KSHV) initiates these processes by causing cells to secrete growth and invasive factors.

Since there is no cure for herpesviruses, the discovery of this gene's role in the growth and spread of the sarcoma raises the possibility that a treatment aimed at blocking K1's function may help to slow and contain the disease, the research team reported.

The new findings appeared in the April 14 issue of the journal Cancer Research.

"If you target the initiation process then you might prevent growth and metastasis from occurring," said Dr. Blossom Damania, assistant professor of microbiology and immunology at UNC's School of Medicine. She is the study's senior author and a member of the UNC Lineberger Comprehensive Cancer Center.

Previous research has found that K1, when inserted into normal cells, can make them cancerous. In addition, others have shown that mice bred to express this gene develop skin lesions.

The UNC research shows for the first time how K1 does this in different cell types, Damania said. Kaposi's sarcoma is an angiogenic tumor, meaning that the tumor can recruit blood vessels to the tumor site, and the sarcoma is also known to metastasize. Damania's research team investigated the action of K1 in blood vessel endothelial cells and skin epithelial cells.

"We observed that K1 up-regulates vascular endothelial growth factor, VEGF. This growth factor leads to greater recruitment of blood vessels to the site of the tumor, which supplies nutrients and allows the tumor to grow," she said.

The UNC research also showed that K1 increases expression of matrix metalloproteinase-9, an enzyme that breaks down the supporting tissue of cells and has been linked previously with the VEGF pathway and metastases.

"Both these factors are used in normal remodeling processes like wound healing, but cancer cells often usurp these pathways in order to grow and metastasize, or spread," Damania said. KSHV is a member of the herpesvirus family. Eight herpesviruses currently are known to be prevalent in humans.

"In normal, healthy individuals, the immune system keeps these viruses in check. However, if we become immune-suppressed, either through diseases such as AIDS, or by taking immuno-suppressant drugs as a transplant patient, then these viruses can replicate and spread," Damania said.

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