Study: Smell receptors help progress of prostate cancer

By Allen Cone  |  May 31, 2018 at 10:27 AM
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May 31 (UPI) -- A cell receptor responsible for the sense of smell plays a critical role in prostate cancer progression, according to a study.

Researchers at the Duke University School of Medicine found that the receptor, called OR51E2, caused the cancer to morph into the more aggressive, "castration-resistant" form of the disease. Their findings were published this week in Frontiers in Oncology -- Genitourinary Oncology.

"By identifying molecules that can activate or block this receptor, we could change the course of prostate cancer," senior study author Dr. Hiroaki Matsunami, a professor of molecular genetics and microbiology at Duke's School of Medicine, said in a press release.

The researchers believe blocking the receptor with specific molecules or even with specific scents could provide a new way to treat prostate cancer.

"When you smell a specific odor, the molecules you inhale go into your bloodstream. So one day, we may be able to use an odorant to cure prostate cancer -- though it's not possible yet," Matsunami said.

Prostate cancer is the most common non-skin cancer among American men, mainly those older than 65, according to the Centers for Disease Control and Prevention. In 2014, 172,258 men in the United States were diagnosed with prostate cancer and 28,343 died from the disease.

About 25 years ago, scientists found olfactory receptors were appearing in lungs, liver, skin, heart, testes and intestines.

These receptors are among proteins called G protein-coupled receptors, or GPCRs, which act by a lock and key mechanism. When the "key" fits into the receptor's "lock," it causes biochemical reactions that lead to the brain recognizing the scent, such as that of freshly cut grass.

The Duke researchers have identified the molecular keys -- or "ligands" -- that activate more than 50 olfactory receptors involved in smell and other senses.

Lead author Dr. Tatjana Abaffy, a research assistant professor working with Matsunami, studied the olfactory receptors outside the nose.

Abaffy made a virtual model of the olfactory receptor and screened 2,516 human metabolites, selecting the ones most likely to unlock the virtual receptor. She studied the 100 most promising candidates and added them to living cells to find ones that activated the receptor.

Two dozen ligands, including a steroid called 19-hydroxyandrostenedione, or 19 OH-AD, made the cancer cells take on the characteristics of neuroendocrine cells. In prostate cancer deaths, they are characterized by an increased number of these cells.

"The typical therapy for patients with prostate cancer involves eliminating cancer-fueling hormones like testosterone by chemical or surgical castration," Abaffy said. "This approach slows down the cancer, but resistance typically develops after a year or two, resulting in castration-resistant prostate cancer. We believe the olfactory receptor is involved at this stage of the disease."

In addition, cancer cells secrete 19 OH-AD, which is involved in the chemical conversion of testosterone into estrogen and leads to their own progression.

The process stalled when she eliminated the olfactory receptor from the cells -- 19 OH-AD lost its effect.

Researchers are conducting experiments with the other compounds uncovered in this study to test their efficacy as well.

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