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
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
“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