Cancer REsistance of arctic Species

Although the aetiology and curation of cancer in humans and laboratory model organisms has received ample attention, many aspects of cancer remain poorly understood and seriously understudied. For instance, it is now widely recognized that cancer does not only affect humans but occurs in nearly every species in the animal kingdom, from hydras to whales⁠. However, despite a growing interest, our knowledge of cancer in wildlife has remained extremely limited until recently. Recent publications demonstrate the omnipresence of cancer but reveal substantial differences in cancer prevalence/mortality across major mammalian orders. Strikingly, a few species appear to be naturally resistant to cancer progression. Given that these non-standard experimental models may have evolved different natural anti-cancer mechanisms and that the limited research conducted to date has already provided considerable information, further investigation of cancer in wildlife promises extremely valuable advances, potentially leading to the development of innovative and reduced-adverse effects of healthier anti-cancer therapies for humans. Importantly, no study has addressed whether evolution of cancer resistance also provides species with the specific ability of their healthy cells to resist the side-effects of stressors, that are also potentially used in cancer treatments (e.g., irradiations), and have known to have pro-cancer effects.
Seabirds and shorebirds are animal models of interest to study the coevolution of life-history traits and cancer resistance. It is generally intriguing that birds exhibit several physiological parameters that are ageing-prone in mammals, including humans, such as a high metabolic rate or a high blood glucose level and it seems that they evolved a strong resistance to cell immortalization. More specifically, species like the long-lived petrels or oystercatchers present ageing cell mechanisms (elongating telomeres, somatic telomerase activity) that have known to promote cancer in humans. As such, the question of cancer resistance and the nature of their putative mechanisms in birds remained unravelled, and no study to date have addressed its coevolution with life-history traits.
To explore these under-studied aspects of evolution of cancer resistance in animals, CAREaS aims to acquire a unique accurate descriptive database collected simultaneously at the inter-specific level and in a cohort of individuals, on telomere dynamics, telomerase activity and cancer-related proxies that are inexistent in most seabirds and arctic shorebirds. Our overall research hypothesis is that, as a consequence of decreased predation risks due to flying abilities, birds coevolved a slow pace of life (e.g., long lifespan) with specific anti-ageing adaptations (e.g., resistance to high glucose). Such co-evolution of traits might even be more pronounced in Arctic seabirds, as their pace of life is generally slower than that of species in most temperate areas, including seabird populations of the same species. Since cancer is one of the hallmarks of ageing, protective mechanisms against cell immortalization may have emerged as an important mechanism associated to slow paces of life. We expect these mechanisms to be of different nature in small and large seabirds, from the control of telomere length to the activation of genes and the expression of proteins whose anti-cancer role is not yet identified. The present project has three main objectives:

(i) to screen a representative panel of arctic avian species, to establish the continuum of telomere lengths and telomerase activities as well as in vitro cell resistance to irradiation stress. We will establish the correlative links between this continuum and the species life-history traits, as well as with the prevalence of cancer that has been established by our collaborator within birds’ families (M. Giraudeau, pers. com.). Among these species, accessing populations of small petrels will be of key importance. This objective will be conducted across two different field locations, the Ny-Ålesund international research station (Svalbard, 2024, Fulmarus Glacialis with G.W. Gabrielsen) and Middletown Island (Alaska, 2025, 15 species among which the Leach’s Storm Petrel Hydrobatides pelagicus with Dr S. Whelan and Dr S. Leclaire). Access to these birds’ populations will be organized with the named collaborators, who have already agreed to support our program. We aim to obtain 7-10 samples per species, for a total of 20 species.

(ii) to initiate a population study of ringed oystercatchers and establish an age pattern of changes in telomere/telomerase measures and cellular responses to irradiation stress. This will be conducted in our recurrent annual field (2024-2027), near the town of Tromsø, Norway. S. Bourgeon, as the local scientific PI for the oystercatcher program, has already obtained the authorizations for capture and sampling. We plan to start with 30 to 40 captures of adults and chicks per year.

(iii) to investigate differences in contaminant exposure among individuals of the same species. The idea is to determine whether pollutants (and which ones) may change telomerase activity and cell response to stress, i.e., assess to what extent they constitute pro-cancer risks. This will be done in collaboration with J. Gigault to assess the role of microplastics in the modulation of these risks.