Gene involved in sense of smell may play a role in breast cancer metastasis

Not only do our olfactory receptors send smell signals to the brain, but they can also promote the spread of cancer there too.

Researchers at Massachusetts General Hospital (MGH) in Boston have found that the olfactory receptor gene, OR5B21, can cause breast cancer to metastasise to the brain, lungs and bones.

'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', said Dr Bakhos Tannous, director of the Experimental Therapeutics Unit at MGH and co-senior author of the study. 'Our work suggests that the olfactory receptor 5B21 is also a novel oncogene that may figure prominently in cancer progression by driving breast cancer cells to the brain and other sites in the body.'

Dr Litia Carvalho, research fellow at MGH and co-senior author of the study, explained, 'The olfactory receptor family of genes is known to be overexpressed in a variety of cancers, including prostate, melanoma, lung and liver, though its role in breast cancer has been understudied in the past.' As breast cancer is the leading cause of cancer in women, there is a great need to better understand its progression and spread.

The research team used a mouse model of breast cancer metastasis to evaluate the expression of olfactory receptor genes at different sites in the body. They found that in cancer that had migrated from the breast to the brain, lung, and bone, there was increased expression of 20 different olfactory genes. The gene with the greatest expression at all three sites was OR5B21.

When they reduced the expression of OR5B21 using a gene knockout the ability of the cancer to spread in the mice greatly reduced, and the reverse occurred upon increased OR5B21 expression. They found that OR5B21 enhanced metastasis by activating a signalling pathway involved in a process called epithelial to mesenchymal transition, whereby cells gain migratory capacity.

Cancer metastasis from the breast to the brain is the leading cause of death in breast cancer patients, therefore OR5B21 could be a key therapeutic target.

Doctor Tannous concluded, 'Our hope is that using OR5B21 as a target for adjuvant therapy could help fill a huge unmet medical need by preventing breast cancer metastasis to the brain and other organs, and thus prolong survival of patients.'

The study was published in iScience.