Erika Burioli: Mysterious transmissible cancers in mussels

Studying a disease that can be transmitted in mussels might seem like something to laugh at to those with a negative mindset. Erika Burioli, however, takes her subject very seriously. And with good reason. Transmissible cancers in bivalves offer promising avenues for understanding cancer cells. So promising, in fact, that the researcher from 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 able to cross host barriers to spread from one animal to another, outsmarting the immune system," explains Erika Burioli, who studies these cancers in bivalves.

Transmissible cancers also exist—albeit very rarely—in mammals. "We are familiar with the devil facial tumor that has caused the massive decline in Tasmanian devil populations over the past 50 years, and, in dogs, the transmissible canine venereal tumor. The latter, which appeared more than 4,000 years ago, is now widespread throughout the world," says the biologist. The longevity of transmissible cancer cell lines remains a mystery. With no known sexual reproduction, these cells multiply by clonal reproduction, which should gradually lead to an accumulation of deleterious mutations and the extinction of these lines.

The hypothesis—which is the subject of the Hypercan project for which Erika Burioli received ERC funding—is that the persistence of cell lines is favored by mechanisms of hyperploidization of cancer cells, in other words, cells with several extra chromosomes compared to a normal diploid cell. Up to 10 times more DNA copies! "A wealth of DNA copies that would 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 (Cancer transmission in marine creatures worries scientists, Geo, 2019/11). 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 her 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 several samples and farming areas were affected. Thanks to a collaboration with Nicolas Bierne fromISEM and Michael Metzger, and genetic analyses, she demonstrated the transmissible nature of this cancerous strain in mussels. This led to the postdoctoral researcher joining 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 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 lines to spread from South America to the Far East. Then thereistheir rapid proliferation rate, "which is closer to that of a micro-parasite than that of known tumors," the scientist points out. These cancer cells are also capable of manipulating their host, as they have a castrating effect on 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," says 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 showed that these cells have a strong propensity for cell-cell fusion, which partly explains hyperploidy. This discovery is important because it is also relevant to research on human cancers, particularly since many tumors are also hyperploid. This phenomenon remains difficult to study in humans. "In transmissible mussel cancer, it will be easier to highlight the mechanisms that lead to hyperploidy, to follow the evolution of the genome and thus to understand the evolutionary mechanisms at play. It is therefore a very promising model for studying the evolution of cancers," explains the researcher, who is about to launch her project.

With funding from the ERC, Erika Burioli will assemble a team by recruiting an assistant engineer, two postdocs, and a PhD student, but will also devote time to fostering national and international collaborations."I will continue to work with Nicolas Bierne and Michael Metzger, but also with Elizabeth Murchison from the University of Cambridge, who is studying transmissible cancer in dogs and Tasmanian devils,"says Burioli, who has gradually moved away from applied research to immerse herself in fundamental research that is full of mysteries.