Archives
Estrogen interferes with immune surveillance in breast cancer
Diana Yates,
Life Sciences Editor
217-333-5802; diya@illinois.edu
|
Released
1/24/07
CHAMPAIGN, Ill. —
Estrogen is known to enhance the growth and migration of breast cancer
cells. Now researchers at the University of Illinois at Urbana-Champaign
have found that estrogen also can shield breast cancer cells from immune
cells.
In a study published online this week in Oncogene, the researchers report
that estrogen induces the expression of an inhibitor that blocks immune
cells’ ability to kill tumor cells. This is the first study to
identify estrogen’s role in shielding breast cancer cells from
the action of immune cells.
The researchers analyzed estrogen’s role in the cascade of events
that occurs when immune cells, called natural killer cells, encounter
a tumor cell. Under normal conditions, natural killer cells release
granules that contain enzymes, called granzymes, which enter and kill
the tumor cell.
The research team found that when estrogen binds to an estrogen receptor
the complex promotes production of a granzyme inhibitor, proteinase
inhibitor 9 (PI-9). The inhibitor binds the granzyme, preventing it
from initiating the molecular cascade that kills tumor cells.
“It wasn’t known that estrogen could do this in breast cancer
cells,” said principal investigator David J. Shapiro, a professor
of biochemistry in the School of Molecular and Cellular
Biology. “The amounts of estrogen required to do this are
quite small.”
U. of I. graduate student Xinguo Jiang also found that when breast cancer
cells that contain very high levels of estrogen receptor protein are
exposed to low levels of estrogen, they produce large quantities of
the granzyme inhibitor and become highly resistant to immune attack.
The researchers were able to show that estrogen’s effect on PI-9
production was the sole mechanism by which estrogen interfered with
the natural killer cells’ ability to kill off breast cancer cells.
They did so by blocking PI-9 production in the breast cancer cells exposed
to estrogen. When these breast cancer cells were targeted by natural
killer cells, they were efficiently killed off, even when significant
levels of estrogen and estrogen receptor were present.
Estrogens are known to cause only a few types of cancers, Shapiro said.
PI-9 also has been implicated in other cancers. High levels of PI-9
in some lymphomas, for example, are associated with poor prognoses.
This study demonstrates how basic research can have important and unanticipated
implications for understanding diseases such as breast cancer, Shapiro
said. The finding that estrogens stimulate PI-9 production could eventually
help drug designers develop new tests – and targets – for
breast cancer therapy.
The research team included collaborators from the University of Wisconsin
at Madison.
Editor’s note: To reach David J. Shapiro, call 217-333-1788;
e-mail: djshapir@illinois.edu
