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 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 oestrogen’s role in shielding breast cancer cells from the action of immune cells.The researchers analysed oestrogen’s role in the cascade of events that occurs when immune cells, called natural killer cells, encounter a tumour cell. Under normal conditions, natural killer cells release granules that contain enzymes, called granzymes, which enter and kill the tumour cell.The research team found that when oestrogen binds to an oestrogen 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 tumour cells.”It wasn’t known that oestrogen 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 oestrogen 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 oestrogen receptor protein are exposed to low levels of oestrogen, they produce large quantities of the granzyme inhibitor and become highly resistant to immune attack.The researchers were able to show that oestrogen’s effect on PI-9 production was the sole mechanism by which oestrogen 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 oestrogen. When these breast cancer cells were targeted by natural killer cells, they were efficiently killed off, even when significant levels of oestrogen and oestrogen 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. (Source: Oncogene : University of Indiana : January 2007.)