Rare cancers spreading among sea creatures have scientists perplexed

Some malignancies can jump between different marine species, the latest in series of discoveries that’s changed our understanding of cancer.

A long time ago, though we don’t know how long, a bay mussel somewhere in the Northern Hemisphere developed a leukemia-like cancer. It began as a mutation in a single rogue cell, which copied itself over and over and over again, and spread through the mussel’s hemolymph, the blood-like fluid in its body.

But then the cancer did something it was not supposed to do, or so we thought: It somehow spread to other mussels through the water. Cloning itself again and again in these new hosts, the malignancy continued to proliferate and infect new individuals.

Even stranger still, the disease didn’t remain in bay mussels alone: It’s now been found in two other shellfish species on opposite ends of the world: blue mussels in France, and Chilean mussels in Argentina and Chile.

This finding, described in a paper published Tuesday in the journal eLife, is the latest in a series of studies showing the transmissible cancers are more common than previously believed—especially in the ocean. This new field of research could help us better understand how cancer develops in both animals and humans, as well as illuminate the murky lives of marine creatures.

“The fact that it’s crossing into two new species is quite fascinating,” says Elizabeth Murchison, who studies transmissible cancers at the University of Cambridge, “and concerning.” Besides being environmentally important, mussels are a favorite food of many cultures—although there’s no evidence that eating cancer-infected shellfish has any impact on human health.

Land and sea

Transmissible cancers, which do not naturally occur in people, were first recognized in two land animals in recent decades. In 2006, researchers discovered that a cancer infecting Australia’s endangered Tasmanian devil—called Tasmanian devil facial tumour disease—could be spread when the animals bite each other, which is a normal part of their behavior. More than 80 percent of the animals have since been infected and killed by this contagious disease and a second, very similar transmissible cancer, which threatens the species with extinction.

Also in 2006, scientists discovered that domestic dogs can spread venereal tumors, which cause cancerous masses on their genitalia. Like all transmissible cancers, the cells are identical, and in the case of dogs, derive from a single canine that lived about 11,000 years ago. (Read on: Dogs carry the oldest known living cancer.)

These findings seriously changed our understanding of cancer, which was previously thought to be confined to cell mutations within individuals. Though various types of viruses can cause damage and pave the way for cancer, such as human papillomavirus (HPV) or feline leukemia virus in domestic cats, it was a shock to find that individual cancer cells could spread among a population.

In the last decade, researchers have found another half dozen cancers that infect shellfish. Michael Metzger, lead author of the new paper and a researcher at Pacific Northwest Research Institute in Seattle, has identified several of them, including one in a British Columbia population of bay mussels (Mytilus trossulus).

A couple years ago, he began collaborating with labs in France and Argentina, which had discovered a new type of cancer in local mussel populations; these cancer cells stick out as unique under the microscope due to their oddly round appearance. What Metzger first expected to be separate cancers turned out to be the same: the diseases in the French blue mussels (Mytilus edulis) and the Chilean mussels (Mytilus chilensis) were identical—and clearly derived from bay mussels, because the cancer cells retained the genetic signature of that species.

But bay mussels only live in the Northern Hemisphere, along the coasts of North America and Europe. (The cancer was also distinct from another type Metzger’s group had earlier identified in M. trossulus.)

None of these mussels live in equatorial areas, so the disease had to have leapfrogged the tropics by attaching to ships or stowing away in ballast water, Metzger explains.

“It’s pretty intriguing that this single cancer clone... has spread across an ocean,” says Murchison, who was not involved with the eLife paper. “Probably we should be paying more attention to the potential for these cancers to be spread by human activity.”

Branching out

Similar transmissible cancers, all infecting the hemolymph and broadly similar to leukemia, have been discovered in softshell clams, such as Mya arenaria, and cockles, a type of shellfish found throughout Europe, including the species Cerastoderma edule. Metzger and colleagues also found that one cancer infecting golden carpet shell clams (Polititapes aureus), actually first arose in pullet carpet shells, a similar shellfish also found in Western Europe.

That was the first evidence that these cancers can jump between species. But this latest finding is even more extraordinary, as it’s spread to two new species.

Though these mussels are closely related, and thus likely have similar vulnerabilities, “we don’t know what the barrier is,” Metzger says. It’s likely the cancer cells spread by being released and taken up in shellfish when they filter debris through their bodies, a normal part of their biology. But other than that, how the disease proliferates is a mystery.

So far, it doesn’t seem like the cancer is devastating to the animals’ populations, though it’s often fatal to the infected individuals. Metzger says the newfound cancer in blue and Chilean mussels was found to infect somewhere around 10 percent of local populations.

“Right now, we don’t really know how big of a threat it would be,” he says. “It doesn’t seem to be wiping out populations.” ‘

Ecological concerns

But these are widespread species, commercially important varieties commonly eaten by people and other wild species. Though harmless to humans, scientists worry that such cancers could have serious impacts in other species—and since scientists have just begun identifying these diseases, they are likely much more prevalent.

“I am very concerned about the ecology,” says Jose Tubio, who studies these types of marine transmissible cancers at Spain’s Center for Research in Molecular Medicine and Chronic Diseases. Tubio’s group got a large grant from the European Research Council to identify new types, and already, they’ve found five unique, new cancer in cockles—research that’s yet to be published.

“It’s likely that [many] bivalve species have their own transmissible cancers,” Tubio says, “but we don’t have a good understanding of what the impacts are.”

Beata Ujvari, a researcher at Deakin University in Victoria, Australia, says that cancers could add to the threats facing marine life, and could be exacerbated by lowered ocean oxygen levels and higher temperatures due to climate change, conditions which cancer cells prefer.

The intentional or accidental movement of shellfish between areas threatens to introduce new cancers that could have serious impacts, Tubio adds.

Cancer, of course, usually arises from a mutation within a body’s cells, and if the immune system doesn’t recognize and destroy it, it can grow into a tumor. But most of the time, a single tumor is not deadly—cancer typically kills by spreading through the body, a process known as metastasis.

But in these spreading cancers, “it’s almost like metastasis beyond a single host,” Murchison says.

“Understanding how cancer cells survive in transport... could potentially unlock the secrets of metastatic cancer cells,” Ujvari says.

“Studying the underlying mechanisms could contribute to our general understanding of immune escape in cancer,” which could have applications for any species impacted by the disease—including humans, she says.

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