BIVALVE Transmissible Neoplasia
Transmissible cancers are probably the most extensively studied neoplastic disease in the wild. The pathogens are rogue, malignant cell lines that have derived and deviated directly from the host or from a closely related species and have acquired the capacity to spread between individuals and in certain cases, across species. Currently, nine transmissible cancers (one in dogs, two in Tasmanian devils (Sarcophilus harrisii), and six in six bivalve species), have been recorded in the wild, but their real abundance could be underestimated (Ujvari et al., 2016). Among them, Disseminated Neoplasia (DN, also called hematopoietic or hemic neoplasia) has been known to affect several bivalve species such as clams, oysters and cockles across the world since the 1960s (Hamede et al., 2020). While originally a retrovirus or retrotransposon aetiology was suspected (Oprandy and Chang, 1983), evidence is now accumulating showing that DN is caused by malignant transmissible cell lines able to pass from one organism to another (Riquet et al., 2017; Metzger et al., 2015, 2016). DN is caused by excessively proliferating cells of the haemolymph that invade the circulatory system and eventually cause the death of bivalves. Horizontal transmission of malignant cells has been demonstrated in soft-shell clams (Mya arenaria), in mussels (Mytilus trossulus, M. edulis, M. chilensis), cockles (Cerastoderma edule), and inter-species contagion was observed in the golden carpet shell clams (Polititapes aureus) where the cancer cells derived from another species, the pullet shell clam (Venerupis corrugata) (Metzger et al., 2016).
As transmissible cancers are seemingly rare (but see Ujvari et al., 2016), it is easy to overlook their ecological and evolutionary impacts. However, the tale of the Tasmanian devils should be a cautionary sign. Only 30 years ago nobody would have predicted that a clonal cell line that spreads as an allograft would push the once abundant Tasmanian devils to the brink of extinction (Hawkins et al., 2006, Hamede et al., 2009), and that 25 years later a novel independent cancer lineage would emerge in the same species (Pye et al., 2016). The recent recognition of widespread contagious cancer cell lines in marine environments raise major questions and especially about their origin, ecological and evolutionary impacts and how to manage and mitigate them. On the other hand, transmissible cancers among bivalves stand for a unique biological system, which is different from the traditional vision for humans of a disease peculiar to each individual. However, this is striking to note that it has not yet been considered as new tool for research in cancerology.
In this project, a multidisciplinary approach will be used at the interface of ecology, oncology, pharmacology, genetic, ecotoxicology, cellular and evolutionary biology to establish a model system at the LIENSs for long-term studies of transmissible cancer in Macoma Balthica in collaboration with Katarzyna Smolarz from the University of Gdansk, Poland (https://www.researchgate.net/profile/Katarzyna-Smolarz).
Transmissible cancers in bivalves show some unique characteristics that make them potentially more susceptible to interact with pollutants. For example, as DN are tumours occurring in aquatic environments, DN cells are in direct contact with marine pollutants. While preliminary results suggest an increase of DN prevalence in polluted habitats, the mechanisms (decrease of host immune capacity, increase of DN transmission and/or virulence) has never been investigated. We are investigating if and how exposure to pollutants might affect the survival and transmission of DN cells in water (Survival and transmission experiments). If modified, this should strongly impact the transmission of the disease between individuals, the dynamic of the disease through time and the probability to observe DN epizooties. Second, we will investigate the evolution of resistance against this transmissible cancer in different bivalve populations in the gulf of Gdansk.