A Highly Accurate Inclusive Cancer Screening Test Using Caenorhabditis elegans Scent Detection
Cancer, in almost all its forms, is an age associated disease. A given cell accrues genetic damage over time until it breaks free of the molecular shackles that maintain a healthy homeostasis. As our molecular safeguards are numerous this process takes time which explains why incidence of cancer increases almost exponentially with age (1). The intrinsic problem with a progressive, (and initially) slow moving disease is that it can remain asymptomatic and therefore undetected until it is too extensive to treat effectively. Melanoma is a excellent example as 95% of patients diagnosed with stage 1A melanoma will live for more than 5 years after diagnosis, however, once it has reached stage 4 as few as 5% of people will last the same amount of time (2).
With this in mind, identifying low cost, effective and largely universal methods for early diagnosis of cancer is a central theme in current biological research. Hirotsu et al (2015) attempted to develop what they refer to as the ‘Nematode Scent Detection Test (NSDT),’ which involves using roundworms to sense distinctive odours reported to emanate from tumours.
They began by exposing the nematode species Caenorhabditis elegans to media that had been used to culture either one of a host of cancer cell lines or non-tumourigenic human fibroblasts. Worms were found to be specifically attracted to media used to culture cancer cells and were not attracted to fibroblast conditioned media. Ancillary to this, the authors found that ODR-3 mutant C. elegans showed no attraction to cancer supplemented media. ODR-3, expressed by AWA and AWC olfactory neurones, is central to the attractive component of the worms’ olfactory system. When patients’ samples were used in place of cell lines the same response was observed. Combined, these data indicate that the worms respond specifically to odours generated by the cancer cells.
The authors next looked to determine whether this attraction could be manipulated for clinical use. When offered urine from patients with cancer or from tumour-free individuals worms were again found to be specifically attracted to the samples from cancer patients. This was true even of urine from early stage individuals. Using calcium imaging they demonstrated increased activity of AWA and AWC neurones in response to patient samples; confirming a role for the olfactory system in detecting cancer specific odours.
Using 460 urine samples, 242 of which were from cancer patients, the authors sought to establish the sensitivity of the NSDT. Stringent analysis found that the NSDT had a sensitivity of 95.8% and whilst this decreased with earlier stage cancers, their test was considerably more sensitive than other established markers. The test was also not influenced by the sex of the patient, other physical complaints or their medical regiment.
To summarise, Hirotsu and colleagues have identified and begun to optimise an innovative, novel, non-invasive method for identifying cancer at early stages. Nematode worms are easily maintained in laboratories around the world where the serve as a popular model organism. They therefore present themselves as a simple low cost tool in cancer diagnosis. However, more work is required to distinguish the specific odours produced by cancer cells. Additionally, the worms cannot indicate the organ from which the cancer originates and will have to be combined with other tests. Despite these caveats the future of the humble nematode as a diagnostic tool looks promising.
HeLa (cancer) cells captured using 2-Photon fluorescence
Thomas Deerinck of the National Center for Microscopy and Imaging Research, La Jolla, CA, USA