Sense Of Smell Responsible For Aggressive Prostate Cancer?
Activating an olfactory receptor in prostate cancer cells causes them to morph into a more aggressive form.
Given that olfactory receptors are largely responsible for our sense of smell, it may surprise you to learn that they don’t exist exclusively in the nose. Their role in organs such as the lungs, liver, skin, heart, testes, and intestines is still an unknown. As with most receptors, they are only activated by certain molecules. Over 50 of these molecules have been identified by Hiroaki Matsunami’s lab at Duke University School of Medicine.
One particular receptor, OR51E2 is present in unusually high levels in prostate cancer cells. So much so, that it is also known as PSGR (Prostate-Specific G Protein-Coupled Receptor). Tatjana Abaffy, a member of Matsunami’s lab, modelled the receptor to try identifying the kinds of molecules that might activate it. The 100 most promising candidates, where then added to living cells to measure for a response.
19 OH-AD (19-hydroxyandrostenedione) was one of a small group of molecules that were found to cause cancer cells to take on the characteristics of neuroendocrine cells. This is exactly what happens when prostate cancer progresses into the very aggressive castration-resistant prostate cancer.
“The typical therapy for patients with prostate cancer involves eliminating cancer-fuelling hormones like testosterone by chemical or surgical castration,” said Abaffy, who is lead author of the study. “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.”
Abaffy also found that cancer cells secrete 19 OH-AD, which acts as a critical intermediate in the chemical conversion of testosterone into oestrogen, essentially feeding their own progression. But when she eliminated the olfactory receptor from the cells, 19 OH-AD lost its effect, and the progression stalled.
“By identifying molecules that can activate or block this receptor, we could change the course of prostate cancer. When you smell a specific odour, 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.
With yesterday’s news that long noncoding RNA has a significant impact on prostate cancer progression, it’s starting to look like important advances are being made in our understanding of the mechanisms of the disease.