Cancer is widespread in the animal kingdom. It can affect different animals – from fish to mammals – and even existed in dinosaurs. Some species develop cancers that are very similar to humans, while others are affected by a rare, contagious form of the disease. At the other end of the spectrum, there are some species that rarely get cancer e.g. whales.
Although documented under laboratory conditions, naturally occurring transmissible contagious cancers with no underlying pathogen infections are rare in the wild. Nonetheless, inter-individual transmission of cancer cells represents an intriguing host-pathogen system, with significant ecological and evolutionary implications. In this blog, we explore transmissible cancers and the evolutionary dynamics between transmissible cancers and their hosts.
What are transmissible cancers?
Infectious agents come in many forms. They are typically grouped into five distinct classes: viruses, bacteria, fungi, parasites and prions. Cancer is not normally on this list. Some infectious agents like HPV and HTLV-1 can cause cancers in infected hosts. However, these cancers are generated within each new individual. Cancer is usually considered a self-limiting disease – it either regresses or it kills its host. Death of the host marks the death of the cancer lineage. But this is not always the case. So far researchers have only identified three transmissible cancers.
A transmissible cancer is a cancer cell or cluster of cancer cells that can be transferred between hosts without the involvement of an infectious agent. Although the vast majority of cancer cells die with their host, evolutionary principles predict the existence of cancer cell lineages that can escape death. These lineages become contagious, acquire higher fitness and consequently are favoured by selection. Once the cancer cells have adapted to the normal barriers that prevent host-to-host transmission, they are subject to the evolutionary dynamics of infectious agents. It has been proposed that transmissible cancers have existed since the transition to multicellularity. Contagious cancers represent an important, but so far understudied, selective force during organismal evolution. Therefore, it is considered an important component of many ecosystems.
Naturally occurring transmissible cancers
Transmissible cancers have been identified as spreading within two vertebrates, dogs (Canis lupus familiaris) and Tasmanian devils (Sarcophilus harrisii), and also multiple independent lineages of transmissible cancers in several species of bivalves.
Canine transmissible venereal tumour
Canine transmissible venereal tumour (CTVT) was first described by a veterinarian in London in 1810. It was also experimentally transplanted between dogs in 1876. However, it was not identified as a contagious cancer (descended from a single lineage) until 2006. Previous studies have proposed that the cell line arose 11,000 years ago. Most recently, the source has been placed in a population of Native American dogs. CTVT spreads as a sexually transmitted infection in feral dog populations throughout the world. It infects animals in at least 90 countries on all continents except Antarctica. The cancer is mostly localised on the external genitalia, but in rare cases it can also manifest on the face. It typically regresses on its own but can be treated easily using chemotherapy drugs such as vincristine.
The concept that this tumour is naturally transmissible came from three important observations:
- CTVTs can only be experimentally induced by transplanting living tumour cells
- The tumour karyotype is aneuploid but has characteristic marker chromosomes in all tumours collected in different geographic regions
- LINE-1 insertion near c-myc has been found in all tumours examined so far
The Tasmanian devil facial tumour disease
The first observation of a Tasmanian devil suffering from devil facial tumour disease (DFTD) was in 1996 in north eastern Tasmania. This first lineage is often now referred to as DFT1. The second and independently risen lineage (DFT2) was discovered in 2014 in D’Entrecasteaux Peninsula. Both diseases present as large ulcerating tumours around the face and jaws, but DFT2 tumours often spread to other parts of the body. Similarly to CTVT, both diseases spread from physical contact when devils bite each other. DFT1 and DFT2 cells are genetically, chromosomally and histologically different. The presence of chromosome Y in DFT2 and remnants of an X chromosome in DFT1 indicate that the older cell line emerged in a female devil and the younger from a male. Transcriptomic analysis has revealed that classical DTFD likely originated in Schwann cells. The cell type origin of DFTD2 is unknown.
Bivalve transmissible neoplasias
Abnormal proliferation of cells in bivalve haemolymph (circulatory fluid) has been widely described since the 1960s. Various disseminated neoplasia have been reported in the soft-shelled clam (Mya arenaria), the mussel (Mytilus trossulus), the cockle species (Cerastoderma edule) and the golden carpet-shell clam (Poltitapes aureus). As multiple lineages of transmissible cancers are spreading through multiple bivalve species, these diseases are known as bivalve transmissible neoplasias (BTN). The origin of disseminated neoplsias is unclear. However, researchers have suggested that the malignant cells stem from haemocyte cells that reside in the animals’ circulatory system.
The distribution of transmissible BTN across continents most likely has been facilitated by a transmission mode that does not require direct contact between individuals. For example, human interference via marine transportation. Neoplastic haemocytes in bivalves are also often aneuploid with an increased DNA content indicating high chromosomal instability. Neoplastic diseases in bivalves appear at their highest frequency in polluted areas.
Transmissible cancers in humans
While large-scale transmission of cancer has not been observed in humans, transmission between humans has been observed on a small scale in a number of circumstances. This is often in the context of immune suppression. For example, there was a case of immune suppression leading to transmission of cancer cells in an AIDS patient who acquired neoplastic cells derived from the cells of a dwarf tapeworm.
There have only been a few cases of human cancer transmission without immune suppression. For example, there was a case of a surgeon who accidentally introduced a cancer into his own hand during an operation. Within five months a tumour developed on his hand but was later excised and did not recur. Additionally, a laboratory worker accidentally bruised herself with the needles she was using to inject colonic cancer cells into mice. She developed a small tumour on her hand within two weeks.
There have also been cases of human cancer transmission during transplantation. For example, in 2007, four people received different organ transplants from a 53 year old woman who had recently died from intracranial bleeding. The organ donor showed no signs of cancer upon medical examination. However, the organ recipients later developed metastatic breast cancer and three died from the cancer between 2009-2017. The risk of tumour transmission is between 0.01 and 0.05% for each solid organ transplant. This low incidence implies that current practices of donor screening for malignancy are effective. Nonetheless, once transmitted, the mortality rate is high. Improvements could be made by including additional data from national transplant registries with a more detailed donor assessment. As a result, this would enhance expert’s knowledge of tumour transmission in organ transplantation and help make well‐informed assessments of donor risk.
Transmissible cancers appear to be limited by two main factors: immune recognition and physical barriers to the spread of cells. This draws parallels with conventional cancers and their own evolutionary pressures to evade immune recognition and metastasise. Currently, transmissible cancers are known to spread through only a few natural animal populations but with further study more examples are likely to be uncovered. It is thought that transmissible cancers have been developing and spreading since the beginning of multicellularity. Although rare in nature, transmissible cancers represent a fascinating and important eco-evolutionary phenomenon that may provide novel insights into human cancers.
Image credit: Photo by Meg Jerrard on Unsplash