Erika Burioli: Mysterious Contagious Cancers in Mussels

Studying a transmissible disease in mussels might seem like a source of ridicule to those with a twisted sense of humor. Erika Burioli, however, takes her subject very seriously. And for good reason. Transmissible cancers in bivalves open up promising avenues for understanding cancer cells. So promising, in fact, that the researcher at the Host-Pathogen-Environment Interactions (IHPE) laboratory was awarded a €1.5 million ERC grant in September 2023.“Transmissible cancers are astonishing biological entities. The cells involved are capable of crossing the host’s barriers to spread from one animal to another, evading its immune system,” explains Erika Burioli, who studies these cancers in bivalves.

Transmissible cancers also exist—albeit very rarely—in mammals.“We know of the Tasmanian devil facial tumor, which has caused a massive decline in Tasmanian devil populations over the past fifty years, and, in dogs, the canine transmissible venereal tumor. The latter, which appeared over 4,000 years ago, is now widespread throughout the world,” says the biologist. The longevity of these transmissible cancer cell lines remains a mystery. With no known sexual reproduction, these cells multiply through clonal reproduction, which should gradually lead to an accumulation of deleterious mutations and result in the extinction of these cell lines.

The hypothesis—which is the focus of the Hypercan project for which Erika Burioli received ERC funding—is that the persistence of cell lines is facilitated by mechanisms of hyperploidization in cancer cells, that is, cells with several extra chromosomes compared to a normal diploid cell. Up to 10 times more copies of DNA!“An abundance of DNA copies that would help limit the effect of deleterious mutations and generate genetic diversity,” explains the researcher.

By chance

It was not until 2015 that the first transmissible cancer in bivalves was discovered by American researcher Michael Metzger of the Pacific Northwest Institute in Seattle (The transmission of cancer in marine creatures is a concern for scientists, Geo, November 2019). Since then, seven other transmissible cancer strains have been identified in bivalves, including those that infect marine mussels of the genus Mytilus, which Erika Burioli discovered by chance while working on diseases in aquaculture. The researcher began her scientific career at the Faculty of Veterinary Medicine at the University of Bologna, where her thesis focused on epidemics in oyster farms.

She continued this applied research as a postdoctoral fellow at the Labeo laboratory in Caen in 2017, where one day a mussel farmer brought her samples from his decimated farm. After studying them closely, she diagnosed the presence of cancer—a type of leukemia—with the characteristics of an infectious disease, as multiple samples and farming areas were affected. Through collaboration with Nicolas Bierne ofISEM and Michael Metzger, along with genetic analyses, she demonstrated the transmissible nature of this cancerous lineage in mussels. This led the postdoctoral researcher to join the IHPE laboratory in Montpellier in 2019 for the ANR Transcan project, to study the phenotypic characteristics and epidemiology of these cancers.

The study of these cancer cell lines has revealed many surprises. First, their ability to survive: they remain alive for more than three days in seawater, which is a long time for an isolated cell. This resistance allows the spread of lines present from South America to the Far East. Next, their rapid rate of proliferation,“which is closer to that of a micro-parasite than to that of known tumors,” notes the scientist. These cancer cells are also capable of manipulating their host, as they have a castrating effect in the infected organism from the earliest stages of infection,“presumably to recover as many resources as possible for proliferation—resources that would otherwise be allocated to reproduction,” explains Erika Burioli.

Cell-cell fusion

“What intrigues me today are the evolutionary mechanisms at work in these lineages, which are capable of persisting for so long in host populations.” Thanks to Muse “ERC Springboard” funding, which enabled her to work with a master’s student, she demonstrated that these cells have a strong propensity for cell-cell fusion, which partly explains the hyperploidy. This discovery is significant because it also has implications for human cancer research, particularly since many tumors are also hyperploid. This phenomenon remains difficult to study in humans.“In the case of transmissible cancer in mussels, it will be easier to shed light on the mechanisms leading to hyperploidy, track the evolution of the genome, and thus understand the evolutionary mechanisms at play. It is therefore a very promising model for studying the evolution of cancers,” explains the researcher, who is preparing to launch her project.

With funding from the ERC, Erika Burioli will assemble a team by hiring an engineering assistant, two postdocs, and a PhD student, while also dedicating time to fostering national and international collaborations.“I will continue to work with Nicolas Bierne and Michael Metzger, as well as with Elizabeth Murchison from the University of Cambridge, who studies transmissible cancer in dogs and Tasmanian devils,”notes Burioli, who has gradually moved away from applied research to immerse herself in fundamental research that is undeniably full of mysteries.