Are Tumours Spreading? Cancer as an infectious disease

This week saw one of the strangest scientific discoveries in the last few months. An article was published on 5th November in the New England Journal of Medicine detailing a case study of a HIV positive man presenting with fever and weight loss who, after several months of unsuccessful treatment, passed away from unknown causes1. Extensive post mortem analysis found malignant tumorous masses, in his lungs and lymph nodes, of non-human origin. Whilst this is beginning to sound like the opening plot of a cheesy horror film, the cells were found to originate from a species of tapeworm, known as Hymenolepis nana (or Dwarf tapeworm), endemic to the region. To my knowledge, this is the first documented case of zoonotic transmission of cancer. Cancer is typically a non-infectious disease, however, there are some notable examples of transmission of tumorigenic cells between individuals of the same species.

Transmission of tumours from human to human is not uncommon. Patients who receive organ donations regularly inherit previously unidentified tumours from their donors2. The progression of the tumours is aided by the necessity for transplant patients to take immuno-suppressive drugs to prevent organ rejection. However, the circumstances don’t have to be as extreme as an organ transplant. Children are capable of contracting  cancer in utero from their mother3. The high level of genetic similarity between mother and child, and the lack of immunological education in the early foetus makes vertical transmission possible albeit rare. Perhaps the most bizzare example of human to human transmission is the case of a surgeon who became infected with the tumour of a patient he was operating on after sustaining an injury during the operation4.

Sharing of tumours can also be seen in other species. In both dogs and Tasmanian devils transmission of cancer cells between individuals is highly common. In the case of dogs the cells are transmitted sexually, whilst in Tasmanian devils common face biting behaviour allows for the transfer of malignant cells. Due to incredibly low genetic diversity within both species the transmitted cells are not recognised as foreign and therefore do not trigger the host’s immune system5.

But how did our Colombian man become host for tape worm tumours? Well, his HIV status appears to be the key factor. He had been diagnosed as HIV positive nearly eight years prior to his death and was potentially infected many years before that. At this late stage of infection his ability to generate an immune response would have been severely compromised. This had serious consequences, firstly it may have caused the tapeworm to develop abnormal growths normally limited in healthy people. Secondly, it prevented his body from recognising and responding to the invasive cells that broke free from the worm and disseminated throughout his body. Had the HIV virus not made him severely immunocompromised his immune cells would have rapidly engulfed and destroyed the invading worm cells.

So, should we start thinking of cancer as an infectious disease? In the developed world the low exposure to parasitic worms and the relatively low HIV rate mean the chances of a similar case occurring in say London or Rome are almost non-existent. However, in the developing world similar cases may be highly prevalent with these events previously being unidentified due to limitations in local healthcare. Identifying zoonotic cancers may be crucial when considering treatment options in the future. Furthermore, the potential to develop tumours adds a further dimension of risk to infection with parasitic worms.

References:

  1. Muehlenbachs. N Engl J Med (2015) 373, 1845-1852
  2. Penn. Ann Transplant (1997) 2, 7-12
  3. Osada. Cancer (1990) 65, 1146-1149
  4. Gartner. N Engl J Med (1996) 335, 1494-1497
  5. Murchison. Oncogene (2009) 27, S19-S30

N.B. unfortunately I couldn’t find the original source of the image to credit

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Sniffer Worms: A Universal Effective Low Cost Method for Detecting Cancer?

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.

References:

(1) Cancer Incidence By Age – CRUK

(2) Melanoma Survival Stats – CRUK

(n) Hirotsu et al (2015) PlosONE, 10doi:10.1371

Image Credit:

HeLa (cancer) cells captured using 2-Photon fluorescence

Thomas Deerinck of the National Center for Microscopy and Imaging Research, La Jolla, CA, USA