Erika Burioli: Mysterious transmissible cancers in mussels

Studying a transmissible disease in mussels, the ill-placed minds could find it a source of mockery. Erika Burioli takes her subject very seriously. And for good reason. Transmissible cancers in bivalves open up promising avenues for understanding cancer cells. So promising that the researcher from the Host-Pathogen-Environment Interactions ( IHPE ) laboratory obtained an ERC worth 1.5 million 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, by outwitting its immune system ," explains Erika Burioli, who studies these cancers in bivalves.

Transmissible cancers also exist – although very rarely – in mammals. “ We know about devil facial tumor, which caused the massive decline in Tasmanian devil populations over the last fifty years, and in dogs, transmissible canine venereal tumor. The latter, which appeared more than 4,000 years ago, is now widespread throughout the world ,” says the biologist. This 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 lead to 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 lineages is favored by hyperploidization mechanisms of cancer cells, in other words cells with several extra chromosomes compared to a normal diploid cell. Up to 10 times more copies of DNA! “ A wealth of DNA copies that would limit the effect of deleterious mutations and generate genetic diversity ,” explains the researcher.

By chance

It was only in 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 lines have been identified in bivalves, including those that infect marine mussels of the genus Mytilus , which Erika Burioli discovered by chance while working on farm diseases. The researcher began her scientific career at the Faculty of Veterinary Medicine of the University of Bologna, where her thesis focused on epidemics in oyster farms.

Applied research that she continued 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 since several samples and farming areas were affected. Thanks to a collaboration with Nicolas Bierne from Isem and Michael Metzger, and genetic analyses, she demonstrated the transmissible nature of this cancerous lineage in mussels. This gave the postdoctoral fellow the opportunity to join the IHPE laboratory in Montpellier in 2019 for the ANR Transcan project, in order to study the phenotypic characteristics and epidemiology of these cancers.

The study of these cancerous lines is full of surprises. First, their ability to survive: they stay alive for more than three days in seawater, which is a long time for an isolated cell. This resistance allows the propagation of lines present from South America to the Far East. Then their high speed of proliferation, " which is closer to that of a micro-parasite than that of known tumors ," the scientist points out. These cancerous cells are also capable of manipulating their host since they have a castrating effect in the infected organism, from the first stages of infection, " probably to recover the maximum resources to proliferate, resources that would otherwise be allocated to reproduction ," says Erika Burioli.

Cell-cell fusion

" What intrigues me today are the evolutionary mechanisms that occur in these lineages, capable of persisting for so long in host populations ." Thanks to Muse "Tremplin ERC" funding that allowed 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 of interest to research on human cancers, particularly because many tumors are also hyperploid. This phenomenon remains difficult to study in humans. " In transmissible mussel cancer, it will be easier to shed light on the mechanisms that lead to hyperploidy, to follow the evolution of the genome and therefore to understand the evolutionary mechanisms at play. It is therefore a very promising model for studying the evolution of cancers ," explains the woman who is about to launch her project.

With the ERC funding, Erika Burioli will set up a team by recruiting an engineering assistant, two post-docs 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 studies transmissible cancer in dogs and the Tasmanian devil ," emphasizes the woman who has gradually moved away from applied research to immerse herself in fundamental research that is certainly full of mysteries.