Abstract
Chemosensory receptors play a crucial role in distinguishing the wide range of volatile/soluble molecules by binding them with high accuracy. Chemosensation is the main sensory modality in organisms lacking long-range sensory mechanisms like vision/hearing. Despite its low number of sensory neurons, the nematode Caenorhabditis elegans possesses several chemosensory receptors, allowing it to detect about as many odorants as mammals. Here, we show that C. elegans displays attraction towards urine samples of women with breast cancer, avoiding control ones. Behavioral assays on animals lacking AWC sensory neurons demonstrate the relevance of these neurons in sensing cancer odorants: calcium imaging on AWC increases the accuracy of the discrimination (97.22%). Also, chemotaxis assays on animals lacking GPCRs expressed in AWC allow to identify receptors involved in binding cancer metabolites, suggesting that an alteration of a few metabolites is sufficient for the cancer discriminating behavior of C. elegans, which may help identify a fundamental fingerprint of breast cancer.
Highlights
Chemosensory receptors play a crucial role in distinguishing the wide range of volatile/soluble molecules by binding them with high accuracy
We prove that cancer samples activate specific olfactory neurons (AWCs) reliably, and identify a subset of G-protein coupled receptors (GPCRs) that may be involved in this neuronal response
We reported the ability of C. elegans to efficiently discriminate between subjects diagnosed with breast cancer and healthy controls by responding to urine, a bio-fluid that harbors an odor signature that is cancer-specific[32]
Summary
Chemosensory receptors play a crucial role in distinguishing the wide range of volatile/soluble molecules by binding them with high accuracy. Chemotaxis assays on animals lacking GPCRs expressed in AWC allow to identify receptors involved in binding cancer metabolites, suggesting that an alteration of a few metabolites is sufficient for the cancer discriminating behavior of C. elegans, which may help identify a fundamental fingerprint of breast cancer. Altered concentrations in the volatilome have been found in spectra of GC/MS on cancer b iofluids[34,35,36], but, to date, the identification of specific cancer biomarkers through these methods may be problematic given the sensitivity up to the micromolar range and the difficulties in identifying large percentages of the total metabolites which are detected in a biological m atrix[37] Among this high number of molecules, the high sensitivity and specificity of the C. elegans olfactory system (up to the nanomolar r ange23) may guide the identification of the essential metabolic signature of cancer
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