In almost all cases where prostate cancer spreads to other areas of the body, the disease spreads to the bone first. In a new study, researchers reveal the discovery of an enzyme that helps prostate cancer cells to invade bone. Furthermore, certain antidepressant medications may have the potential to block this enzyme.
Study co-author Jason Wu, of Washington State University-Spokane, and colleagues recently reported their findings in the journal Cancer Cell.
According to the American Cancer Society, there will be 161,360 new cases of prostate cancer diagnosed in 2017, and more than 26,000 men will die from the disease.
When prostate cancer cells spread to other body parts – a process known as metastasis – the bone is the normally the first area affected. Around 90 percent of prostate cancer deaths involve bone metastasis.
In the new study, Wu and colleagues uncovered an enzyme called MAOA that prompts a signaling cascade that simplifies the process by which prostate cancer cells spread to the bone.
The researchers came to their findings by introducing human prostate cancer cell lines into mice and analyzing MAOA activity.
The team found that the MAOA enzyme in prostate cancer cells stimulates three proteins to boost the function of osteoclasts, which are bone cells that play a role in the degradation of bone tissue during growth and healing.
“The cancer cells can specifically activate the osteoclasts for bone degradation,” explains Wu. “The experimental phenomenon we’ve observed is actually a lot more bone destruction than new bone formation.”
When the researchers reduced the expression of MAOA in the prostate cancer cells, they found it reduced the cells’ ability to spread to the bone. “On the other hand, if we overexpress this enzyme in prostate cancer cells, we found increased bone metastasis in mice,” says Wu.
In the next part of the study, the researchers tested a drug called clorgyline – a drug once used as an antidepressant that is known to block the activity of MAOA – on prostate cancer cell lines.
They found that the drug prevented MAOA from activating the three proteins that enhance osteoclast function, thereby reducing the prostate cancer cells’ ability to invade and grow in bone.
“Our findings provide a rationale to pursue the new use of these ‘old’ antidepressant drugs to benefit late-stage prostate cancer patients with signs and symptoms of metastasis.”
The researchers note that there are antidepressants in clinical use that work in a similar way to clorgyline, and researchers are currently investigating how these medications affect tumor growth.
“Our studies provide promising results in mice, which merit further investigation, such as adjusting the formulation, dose, and delivery route of MAOA inhibitors, prior to ultimate clinical application,” notes Wu.