Scientists Find New Way to Fight Prostate Cancer That Spreads to Bones

Scientists have discovered that prostate cancer cells use a kind of "invisibility cloak" made of sugar-like molecules to hide from the body's immune system. When cancer spreads to the bones, these molecules become even more powerful, helping tumors grow and survive. Researchers found a new treatment that strips away this cloak, allowing immune cells to find and attack the cancer. Tests in mice showed that the treatment helped the animals live longer.

Prostate cancer is one of the most common cancers in men. In some patients, the cancer spreads — or "metastasizes" — from the prostate to the bones, which makes it much harder to treat. When cancer reaches the bones, doctors have fewer options, and patients often do not survive as long. Scientists wanted to find out why the cancer is so good at hiding in bones and what could be done to stop it.

The researchers focused on special molecules on the surface of cancer cells called sialoglycans. These molecules act like a disguise, sending a signal to nearby immune cells that says "don't attack me." Immune cells normally find and destroy harmful cells, but when they see these sugar-like molecules, they back off and leave the cancer alone. The scientists found that prostate cancer cells — especially those growing in bones — have much higher levels of these molecules than normal, healthy cells.

To study this, the team looked at tissue samples from hundreds of prostate cancer patients. They used seven large collections of cancer tissue, called tissue microarrays, which let them study many patients at once. Their tests showed that the disguise molecules were clearly higher in cancer tissue than in normal tissue. They also found that patients with higher levels of certain molecules called Siglec-7 and Siglec-9 ligands did not survive as long as patients with lower levels.

The scientists also discovered that cancer cells and immune cells in bone tumors both carry matching "lock and key" proteins. The cancer cells carry the sialoglycan "keys," and the immune cells carry the Siglec "locks." When the keys fit into the locks, the immune cells are switched off. This means the cancer has a direct way to shut down the very cells that are supposed to stop it.

To fight back, the research team tested a special engineered protein called E-612. This protein works like a tiny pair of scissors — it cuts the sugar-like disguise molecules off the surface of cancer cells. Without their cloak, the cancer cells could be spotted by the immune system. When scientists used E-612 on cancer cells in the lab, they found that immune cells called natural killer cells were much better at attacking the cancer.

The team then tested E-612 in living mice that had prostate cancer spreading to their bones. The mice that received the treatment lived significantly longer than mice that did not. The treatment also increased the number of immune cells that moved into the tumors. These results suggest the treatment is very promising, though much more research is needed before it could be used in human patients.

The scientists say their study reveals a new target for treating bone cancer caused by prostate cancer. By blocking the Siglec-sialoglycan connection — the lock-and-key system that shuts down immune cells — doctors may one day be able to slow or stop this deadly form of cancer. The research was published in the British Journal of Cancer and involved teams from universities and pharmaceutical companies working together.