Study Upturns Ideas About a Key Molecule in Advanced Prostate Cancer
Research by Brady pathologists has added an important new piece to the puzzle of the immune system’s role in prostate cancer. Even better, it suggests a potential new target for treatment of metastatic disease.
The key player in this discovery is Interleukin-6 (IL-6), a cell signaling molecule that normally is involved in the body’s immune response to bacterial infections and other conditions. “Early evidence for a role for IL-6 in the development and progression of prostate cancer came from studies examining levels of this molecule in the blood of men with metas tatic or hormone-refractory prostate cancer,” says Karen Sfanos, Ph.D., Assistant Professor of Pathology and Oncology. “Studies consistently showed that elevated blood levels of IL -6 were associated with poor prognosis.” Higher levels of IL-6 may also serve as a marker of other problems connected to advanced prostate cancer, such as weight loss and fatigue. Anti-IL-6 drugs, such as siltuxamab, have entered into clinical trials, but so far have not proven as helpful as scientists had hoped.
A recent study conducted by Shu-Han Yu, M.S., a Pathobiology graduate student in the laboratory of Sfanos and Angelo De Marzo, M.D., Ph.D., may shed new light on the role of IL-6 in the development and progression of prostate cancer. It may also help scientists come up with better ways to target this molecule in metastatic disease.
The study set out to answer some important questions about IL-6 in men with advanced prostate cancer, Sfanos says, including: “Precisely when during disease development and progression is IL-6 made, and what specific cell types are responsible for its production? Does IL-6 come from prostate tumor cells, or from other cells?” Until recently, these questions were difficult to assess.
Because the IL-6 protein is rapidly secreted, measuring it was like trying to hit a moving target. In this study, “Shu-Han used a cutting-edge technology called chromogenic in situ hybridization,” Sfanos explains. “This is an assa y that can detect IL-6 genetic material called RNA within a cell befor e it is made into the IL-6 protein that is secreted from the cell. Surprisingly, Shu-Han discovered that IL-6 is not made b y prostate cancer cells in either primary or metastatic disease. These findings are in stark contrast to previously published literature.”
It turns out that IL -6 is not made by prostate cancer
cells in either primary or metastatic disease.
“These findings are in stark contrast to previously published literature.”
It turns out that IL -6 is made by cells in the stroma, the supportive framework of cells surrounding the tumor, and is produced by immune cells and cells called endothelial cells that ar e contained in blood vessels. “Intriguingly, we found that in metas tatic disease, IL-6 production in endothelial cells was distinctly associated with blood vessels in prostate cancer metastases to bone, as opposed to metas tases at other anatomical sites. This might represent a unique mechanism by which IL-6 is involved in prostate cancer progression.” It might also lead to new w ays to target this molecule, and alleviate some of the worst symptoms of metastatic cancer. Other Hopkins investigators involved in the study include Qizhi Zheng, M.D., Jun Luo, Ph.D., and Emmanuel Antonarakis, M.D.