A gene linked in sense smell could play a role in breast cancer spreading to the brain.

Researchers at Massachusetts General Hospital (MGH) discovered that an olfactory receptor gene that aids in the sense of smell may also have a role in breast cancer metastasis to the brain, bones, and lung. According to a research published in iScience, the scientists also showed that blocking the gene OR5B21 greatly reduced the metastasis of breast cancer cells to these organs, suggesting that it could be a key target for future therapy to prevent the disease's spread.

Bakhos Tannous, PhD, director of the Experimental Therapeutics Unit in the Department of Neurology at MGH and senior author of the study, says that "the common perception is that the only role of olfactory receptors, which line the nasal cavity and relay sensory data to the brain, is to recognise odour and smell." "Our findings imply that the olfactory receptor 5B21 is also a new oncogene that plays a role in cancer progression by directing breast cancer cells to the brain and other parts of the body," says the researcher.

With over two million new cases reported each year, breast cancer is the second most commonly diagnosed malignancy after lung cancer and the major cause of cancer in women. Furthermore, breast cancer migration to the brain is the major cause of death from the disease, highlighting the urgent need for new treatment targets to slow or stop its spread.

"The olfactory receptor family of genes is known to be overexpressed in a variety of cancers, including prostate, melanoma, lung, and liver," says Litia Carvalho, PhD, co-corresponding author of the study and an instructor in Neurology at MGH. "However, its role in breast cancer has been understudied in the past." OR5B21 promotes or primes breast cancer cells to metastasis through a signaling pathway that initiates a process known as the epithelial to mesenchymal transition, according to the team's findings in animal models (EMT). Multiple biochemical or phenotypic changes occur in olfactory cells as a result of EMT, including increased migratory potential to distant organs, including the brain.

"Through the signalling pathway NF-B/STAT, this activation translates a wide range of extracellular signals into intracellular instructions, resulting in cell proliferation, invasion, and metastasis," says lead author Mao Li, a graduate student researcher in the Experimental Therapeutics Unit. "Our discoveries are ground-breaking in the field, but further research is needed to figure out exactly how OR5B21 causes metastasis."

In response to the team's observation that downregulating the olfactory receptor resulted in a significant reduction in cancer cell metastasis, future study could lead to a chemical inhibitor of OR5B21. "Our goal is that by targeting OR5B21 as an adjuvant therapy target, we can assist satisfy a big unmet medical need by avoiding breast cancer metastasis to the brain and other organs, and thereby extend patient longevity," Tannous explains.

Reference:

Mao Li, Markus W. Schweiger, Daniel J. Ryan, Ichiro Nakano, Litia A. Carvalho, Bakhos A. Tannous. Olfactory receptor 5B21 drives breast cancer metastasis. iScience, 2021; 24 (12): 103519 DOI: 10.1016/j.isci.2021.103519