Prostate Cancer: Why the Boomerang?

Author: John Monczunski

Treating prostate cancer can be a risky business. In lab studies with animal models, Notre Dame’s Martin Tenniswood has found that the two primary drugs used to treat the disease, flutamide and bicalutamide, in some cases can have a boomerang effect and actually foster cancer spread. “[I]f you don’t kill all of the localized tumor, you are making what is left a lot nastier,” says the Coleman Foundation Professor of Biological Sciences.

Tenniswood’s current work is aimed at understanding why the boomerang effect occurs. A protein called clusterin, which his lab first isolated in 1985, is a prime suspect in the process. Normally clusterin is secreted at low levels and serves as a scavenging agent, cleaning up membranes, he explains. However, when prostate cancer is treated with drugs such as flutamide and bicalutamide, the cells that die secrete more clusterin in the process. Some of the scavenging protein goes to the nucleus, where it prevents DNA repair. Some is flushed into the circulatory system, where it serves as glue sticking together individual cancer cells shed by the tumor into a ball called an embolus.

“If an embolus flows into a tiny capillary it’s more likely to get stuck than a single cancer cell,” Tenniswood explains. Once that happens, the ball of cancer cells releases other proteins, which “chew” their way through the capillary into the underlying tissue where the cancer spreads.

Tenniswood says clusterin is difficult to understand because the protein appears in many different body tissues and responds to many different chemical processes. “Sometimes it appears to be responsible for cell survival, other times for cell death,” the biologist says.
“If we’re able to figure out what clusterin is doing, we may be able to interfere with its activity,” says Tenniswood. That would be good news for cancer patients. If you can prevent emboli, you should prevent spread. And that’s the goal.

John Monczunski is an associate editor of this magazine.