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Researchers Use Rat Stem Cells To Study Kaposi’s Sarcoma Virus

Photo: Tiffany Jones, visiting scholar at the Keck School of Medicine of USC, and S.J. Gao, professor of molecular microbiology and immunology at the Keck School of Medicine of USC (by Jon Nalick)

To understand a virus that causes cancer — and ultimately learn how to beat it — scientists must be able to infect a healthy cell with the virus, keep that cell alive and transform it into a cancerous cell.

Scientists at the University of Southern California (USC) and University of Texas Health Science Center (HSC) at San Antonio have discovered how to do that with the virus that causes Kaposi’s sarcoma, the most common cancer among AIDS patients. The discovery is described in the study, “Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV,” which was published online on Feb. 1 in The Journal of Clinical Investigation.

“Kaposi’s sarcoma persists,” said S. J. Gao, Ph.D., the study’s senior investigator and professor of molecular microbiology and immunology at the Keck School of Medicine of USC. “In underserved populations of Africa, it’s the No. 1 cancer, accounting for up to 30 percent of all cancers in some areas. It’s a very important problem to address, but there has been no good model to study the virus that causes it.”

In 1994, researchers showed that infection by Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma but found that healthy individuals can be infected and show no signs or symptoms. Transmission is not well understood, but infection is thought to be life-long, and becomes of particular concern to those with compromised immune systems.

“We want to understand the mechanism that causes the cell to become cancerous, but we have not been able to make human cells become cancer cells that live and grow forever,” Gao said. “Most healthy cells will die when introduced to stress, like infection. It’s a natural protective mechanism of the cells.”

Gao’s team of researchers tested various types of human, mouse and rat cells. The rat mesenchymal stem cell, which can differentiate into kidney and blood vessel cells, was the only viable model that could be infected with KSHV, kept alive and transformed into a cancer cell.

“There are limitations to using a non-human or human model, but the chief thing is that we now know a cell that can be efficiently infected. Before infection, it is not a cancer cell, and, after infection, it is,” Gao said.

The researchers are now using the cell model to determine what viral products or genes are required to induce Kaposi’s sarcoma, and what cellular components are manipulated by the virus.

“We can use this model to develop a novel therapeutic approach that targets this virus-induced malignancy,” Gao said.

Tiffany Jones, the study’s first author, is a visiting scholar at the Keck School of Medicine of USC. The study was a collaborative project among Gao’s laboratory at the Keck School, the University of Texas Health Science Center at San Antonio, and University of Texas at San Antonio. The research was supported by grants from the National Institutes of Health.
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