Infographic: When Cancers Become Parasites

Above: © MESA SCHUMACHER

So far, only dogs, Tasmanian devils, and four bivalve species are known to carry transmissible cancers, which have varying effects on their hosts.

Host species	Domestic dog (Canis lupus familiaris)	Tasmanian devil (Sarcophilus harrisii)	Bivalves (the soft-shelled clam, Mya arenaria, the mussel, Mytilus trossulus, and the cockle species, Cerastoderma edule, and the golden carpet-shell clam, Poltitapes aureus)
Cancer	Canine transmissible venereal tumor (CTVT)	Devil’s facial tumor disease (DFT1 and DFT2)	Clam disseminated neoplasia
Outcome	GABRIELE MARINO, UNIVERSITY OF MESSINA, ITALY CTVT manifests as tumors on dogs’ genitals (seen here at base of penis) that rarely result in death. It regresses on its own or can be treated easily using chemotherapy drugs such as vincristine.	CAMILA ESPEJO, UNIVERSITY OF TASMANI DFT1 and DFT2 form tumors around the mouth and face that restrict the devils’ ability to feed. These cancers are typically fatal, and have driven devils to the brink of extinction.	Marisa Yonemitsu and Rachael Giersch, Pacific Northwest Research Institute These leukemia cells clog bivalves’ internal organs. While the disease has triggered mass die-offs of soft-shelled clams in the past, today it doesn’t seem to cause severe problems.
Origin	Recent studies have estimated that CTVT arose in one of the first dog populations to inhabit North America some 8,000 years ago. It is believed to stem from a macrophage or another kind of immune cell.	DFT1 is thought to have originated in a devil that lived some 20 years ago. DFT2 is thought to be much younger than DFT1, but its exact age is unknown. Researchers think the cancers stem from Schwann cells, which protect neurons and help repair them after damage.	Not much is known about the origin of disseminated neoplasia in clams, but researchers have suggested that the malignant cells stem from hemocyte cells that reside in the animals’ circulatory system.
Mode of transmission	©istock.com, Oleg_0 CTVT spreads through sexual intercourse.	©istock.com, Parfenov yurii Both devil cancers are thought to spread when the animals bite each other, for instance, during the mating season.	@istock.com, hailshadow Dead individuals are thought to release cancer cells that drift through seawater, infecting other individuals that likely pick them up through filter feeding.

In one of the most extensive studies of devil facial tumor disease (DFT1) to date, an international team of researchers has uncovered a mechanism that drives the cancer’s metastasis and helps it to evade the Tasmanian devils’ immune system.

1	Cancer cells that form DFT1 tumors overproduce transmembrane enzymes known as ERBB receptors.
2	When stimulated by specific proteins—likely EGF and NRG1, which are also overproduced in DFT1 cells—ERBB receptors induce production of a signaling protein and transcription factor called Stat3 and drive its activation.
3	In the nucleus, Stat3 drives the production of genes such as MMP2 that are known to trigger metastasis in humans.
4	Stat3 also binds to and inhibits another transcription factor, Stat1, which normally drives the expression of genes necessary for the generation of MHC class I molecules.

5	MHC class I molecules normally interact with receptors on cytotoxic T cells to discriminate self from foreign cells. By downregulating the production of MHC proteins, DFT1 cells are able to evade detection by the animals’ immune system.
6	Under normal circumstances, cells lacking MHC markers would be detected by natural killer cells (NK), but for reasons that are unclear, devil NK cells don’t react to DFT1.

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