Sniffing Out Cancer Biomarkers

Researchers have used olfactory sensor neurons from mice to detect volatile organic compounds found specifically in urine samples from lung cancer patients.

AsianScientist (May 5, 2016) – A research group in Japan has developed a method for making a prompt, exhaustive isolation of olfactory receptors (ORs) responding to specific odorants, or smells, of interest. This achievement will enable quick and easy, yet exhaustive analysis of ORs responding to specific smells, which previously required a great deal of time and effort.

The findings, published in Scientific Reports, may potentially be applied to biosensors capable of accurately detecting only the desired odorants.

Keeping in mind that each olfactory sensory neuron (OSN) expresses an OR, Professor Shun’ichi Kuroda and Specially Appointed Associate Professor Nobuo Yoshimoto from Osaka University and colleagues from Panasonic Corporation applied OSNs from mice to a microchamber array on a microscope slide. When the OSNs expressed ORs, which in turn responded to odorants, fluorescent markers would indicate the interaction.

The researchers isolated single OSNs responding to specific odorants in a time-lapse single-cell-array cytometric manner and identified the OR gene.

Mouse olfactory epithelium-derived cells were labeled with Fluo4-AM (a), and applied to a microchamber array chip equipped with a flow chamber, followed by brief centrifugation (b). Floating and untrapped cells were removed and stimulated with an odorant (c). OSNs expressing odorant-specific ORs showed transient fluorescence from the increase of intracellular Ca2+ concentration (d). Each activated cell was retrieved (e) and transferred to a polymerase chain reaction plate (f). Credit: Osaka University
Mouse olfactory epithelium-derived cells were labeled with Fluo4-AM (a), and applied to a microchamber array chip equipped with a flow chamber, followed by brief centrifugation (b). Floating and untrapped cells were removed and stimulated with an odorant (c). OSNs expressing odorant-specific ORs showed transient fluorescence from the increase of intracellular Ca2+ concentration (d). Each activated cell was retrieved (e) and transferred to a polymerase chain reaction plate (f). Credit: Osaka University

Using a robot that transferred single cells from an array into individual tubes, the research group succeeded in isolating ORs which respond to three types of volatile organic compounds that are commonly found in urine samples from lung cancer patients: 2-pentanone, pyridine and 2-butanone. Their findings demonstrate the possibility of using specific OR-expressing cells to screen for cancer from biological fluids.

Like OSNs, animal cells expressing ORs responded to the odorant of interest, emitting fluorescence. The researchers predict that their high-throughput OR screening method could be used to isolate other receptors with no known ligands—called orphan receptors—including G-protein coupled receptors, transporters and ion channels.


The article can be found at: Suzuki et al. (2016) Deciphering the Receptor Repertoire Encoding Specific Odorants by Time-Lapse Single-Cell Array Cytometry.

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Source: Osaka University; Photo: Dennis Wong/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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