| U-M
scientists find virus releases molecular brake on roaming cancer
cells
originally posted on February 28, 2001
ANN ARBOR, MI - Scientists
in the University of Michigan Medical School have found a
molecular link between aggressive breast and lymphatic cancers
and the Epstein-Barr virus, which causes infectious mononucleosis.
In a paper published in the March 2001 issue
of Nature Medicine, U-M scientists show how the Epstein-Barr
virus alters the function of a cellular protein that normally
suppresses the movement of malignant cells. When this natural
brake on cell migration is disabled by the virus, cancerous
breast and lymphatic cells are free to metastasize or spread.
"This is the first evidence of a human virus
associated with the development of cancerous tumors targeting
a cellular protein to promote the migration of malignant cells,"
says Erle S. Robertson, Ph.D., who directed the study. Robertson
is an assistant professor of microbiology and immunology in
the U-M Medical School and a researcher in the U-M's Comprehensive
Cancer Center.
"The Epstein-Barr virus is associated with many
human cancers -- including Burkitt's lymphoma, nasopharyngeal
carcinoma, Hodgkin's disease and invasive breast cancer,"
Robertson says.
The virus is very common. More than 90 percent
of adults show signs of previous viral infection. Adolescents
infected with the acute phase of the virus can develop infectious
mononucleosis, but usually the body's natural immune response
forces the virus to revert to its latent phase -- where it
hides inside the nucleus of immune cells called lymphocytes
without producing any symptoms.
Even though the virus is endemic in humans,
Robertson emphasizes that most cells infected by the virus
may never become malignant. Additional genetic factors are
required to trigger development of cancer. Should cancer develop,
however, Robertson says the risk of metastasis may be higher
in individuals previously exposed to the virus.
"People with aggressive forms of cancer are
most vulnerable and should be checked to determine the status
of previous viral exposure when physicians are choosing the
most appropriate treatment for them," Robertson says. "It
also would be wise to closely monitor people with a history
of active Epstein-Barr viral infection for early signs of
cancer."
In the study, Chitra Subramanian, Ph.D., a U-M
research fellow, and Murray A. Cotter II, a U-M graduate student,
investigated a gene from the Epstein-Barr virus called EBNA-3C,
and the protein produced by infected lymphocytes when this
gene is expressed. The EBNA-3C protein was found in all EBV-infected
cancerous lymphocytes in the breast cancer and lymphoma cell
lines analyzed in the study.
U-M researchers discovered that the EBNA-3C
protein binds to a human metastatic suppressor protein called
Nm23-H1, which is found in all human cells. "The interaction
between the two proteins disables Nm23-H1's natural ability
to keep malignant cells in their original location thereby
promoting metastasis," explains Robertson.
"We have mapped the binding site to one region
of the viral protein EBNA-3C and hope in future research to
identify the exact location on the targeted protein," Robertson
says. "Our goal is to find the binding site and discover how
to block the interaction between these two proteins.
"If we succeed, physicians could one day be
able to treat primary breast and lymphatic cancers, as well
as other cancers associated with the Epstein-Barr virus, without
worrying about malignant cells spreading to other parts of
the body."
The research study was funded by the Leukemia
and Lymphoma Society of America and the National Cancer Institute.
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