Folli, Viola, Ferrarese, Giuseppe, Caprini, Davide, Lonardo, Maria Teresa, Pannone, Luca, Ruocco, Giancarlo, Di Rocco, Martina, Martinelli, Simone, Schwartz, Silvia, Milanetti, Edoardo, Lanza, Enrico
[
International Worm Meeting,
2021]
Olfaction is one of the primary mechanisms through which many animals adapt to environmental changes. Olfactory receptors, which in all animals belong to the G-protein coupled receptors (GPCRs) family, play a crucial role in distinguishing the wide range of volatile or soluble molecules by directly binding them with high accuracy. Chemosensation is particularly developed in organisms lacking long-range sensory mechanisms like hearing and vision. The genome of the nematode Caenorhabditis elegans possesses a remarkable number of genes encoding chemosensory receptors, making it able to detect a similar number of odorants as mammals, despite the extremely low number of chemosensory neurons available. Here, we show that C. elegans displays attraction towards urine samples collected from women with breast cancer but avoids those from healthy subjects. This behavior is strongly influenced by the female hormone cycle. Behavioral assays performed on animals in which the AWC sensory neurons were genetically ablated demonstrate an essential role of these neurons in sensing cancer odorants. Calcium imaging experiments on AWC neurons dramatically increase the accuracy in discriminating between positive and control samples (with an accuracy of 97.22%). Also, chemotaxis assays performed on mutant animals harboring individual deletion in genes encoding GPCRs expressed in AWC neurons allow us to identify candidate receptors that are likely to be involved in binding cancer metabolites. This finding suggests that a specific alteration of a restricted number of metabolites is sufficient for the highly accurate cancer discriminating behavior of C. elegans, which may allow in principle to identify the fundamental fingerprint of breast cancer.