Authors: Sophie Tissot, Jordan Meliani, Matthew Chee, Aurora M. Nedelcu, Justine Boutry, Jácint Tökölyi, Rodrigo Hamede, Benjamin Roche, Beata Ujvari, Frédéric Thomas & Antoine M. Dujon

Source: Scientific Reports (Sep 2024)

Abstract

Recent theoretical advances in the One Health approach have suggested that cancer pathologies should be given greater consideration, as cancers often render their hosts more vulnerable to infectious agents, which could turn them into super spreaders within ecosystems. Although biologically plausible, this hypothesis has not yet been validated experimentally.

Using a community of cnidarians of the Hydra genus (Hydra oligactis, Hydra viridissima, Hydra vulgaris) and a commensal ciliate species (Kerona pediculus) that colonizes them, we tested whether tumoral polyps of H. oligactis, compared to healthy ones, played an amplifying role in the number of ciliates, potentially resulting in a higher likelihood of infection for other community members through spillovers. Our results indicate that K. pediculus has a higher proliferation rate on tumoral polyps of H. oligactis than on healthy ones, which results in the infestation of other hydras. However, the magnitude of the spillover differed between recipient species.

This study provides to our knowledge the first elements of proof of concept that tumoral individuals in communities could act as super spreaders of symbionts within and between species, and thus affect biotic interactions and dynamics in ecosystems.

Authors: Margaux Bieuville, Antoine M. Dujon, Nynke Raven, Beata Ujvari, Pascal Pujol, Zahra Eslami-S, Catherine Alix Panabières, Jean-Pascal Capp, Frédéric Thomas

Source: Evolutionary Applications (Oct 2024)

Abstract

While it is recognised that most, if not all, multicellular organisms harbour neoplastic processes within their bodies, the timing of when these undesirable cell proliferations are most likely to occur and progress throughout the organism’s lifetime remains only partially documented. Due to the different mechanisms implicated in tumourigenesis, it is highly unlikely that this probability remains constant at all times and stages of life.

In this article, we summarise what is known about this variation, considering the roles of age, season and circadian rhythm. While most studies requiring that level of detail be done on humans, we also review available evidence in other animal species. For each of these timescales, we identify mechanisms or biological functions shaping the variation. When possible, we show that evolutionary processes likely played a role, either directly to regulate the cancer risk or indirectly through trade-offs.

We find that neoplastic risk varies with age in a more complex way than predicted by early epidemiological models: rather than resulting from mutations alone, tumour development is dictated by tissue- and age-specific processes. Similarly, the seasonal cycle can be associated with risk variation in some species with life-history events such as sexual competition or mating being timed according to the season. Lastly, we show that the circadian cycle influences tumourigenesis in physiological, pathological and therapeutic contexts. We also highlight two biological functions at the core of these variations across our three timescales: immunity and metabolism. Finally, we show that our understanding of the entanglement between tumourigenic processes and biological cycles is constrained by the limited number of species for which we have extensive data.

Improving our knowledge of the periods of vulnerability to the onset and/or progression of (malignant) tumours is a key issue that deserves further investigation, as it is key to successful cancer prevention strategies.

Authors: Frédéric Thomas, James DeGregori, Andriy Marusyk, Antoine M Dujon, Beata Ujvari, Jean-Pascal Capp, Robert Gatenby, Aurora M Nedelcu

Source: Evolution, Medicine, and Public Health (Sep 2024)

Abstract

Tumorigenesis is commonly attributed to Darwinian processes involving natural selection among cells and groups of cells. However, progressing tumors are those that also achieve an appropriate group phenotypic composition (GPC).

Yet, the selective processes acting on tumor GPCs are distinct from that associated with classical Darwinian evolution (i.e. natural selection based on differential reproductive success) as tumors are not genuine evolutionary individuals and do not exhibit heritable variation in fitness.

This complex evolutionary scenario is analogous to the recently proposed concept of ‘selection for function’ invoked for the evolution of both living and non-living systems.

Therefore, we argue that it is inaccurate to assert that Darwinian processes alone account for all the aspects characterizing tumorigenesis and cancer progression; rather, by producing the genetic and phenotypic diversity required for creating novel GPCs, these processes fuel the evolutionary success of tumors that is dependent on selection for function at the tumor level.

Authors: Sophie Tissot, Jordan Meliani, Justine Boutry, Lionel Brazier, Jácint Tökölyi, Benjamin Roche, Beata Ujvari, Aurora M. Nedelcu, Frédéric Thomas and Antoine M. Dujon

Source: Proceedings of the Royal Society B: Biological Sciences (Sep 2024)

Abstract

While most cancers are not transmissible, there are rare cases where cancer cells can spread between individuals and even across species, leading to epidemics. Despite their significance, the origins of such cancers remain elusive due to late detection in host populations. Using Hydra oligactis, which exhibits spontaneous tumour development that in some strains became vertically transmitted, this study presents the first experimental observation of the evolution of a transmissible tumour.

Specifically, we assessed the initial vertical transmission rate of spontaneous tumours and explored the potential for optimizing this rate through artificial selection. One of the hydra strains, which evolved transmissible tumours over five generations, was characterized by analysis of cell type and bacteriome, and assessment of life-history traits.

Our findings indicate that tumour transmission can be immediate for some strains and can be enhanced by selection. The resulting tumours are characterized by overproliferation of large interstitial stem cells and are not associated with a specific bacteriome. Furthermore, despite only five generations of transmission, these tumours induced notable alterations in host life-history traits, hinting at a compensatory response.

This work, therefore, makes the first contribution to understanding the conditions of transmissible cancer emergence and their short-term consequences for the host.

Authors: Emy Beaumont, Jacques Brodeur, Frédéric Thomas, Antoine M. Dujon, Sonia Lupien

Source: Psychoneuroendocrinology (Feb 2024)

Abstract

Background: Schizophrenia is a mental illness that affects approximately 24 million people worldwide. Vulnerability to schizophrenia has been linked by some epidemiologic studies to Toxoplasma gondii (TG), an intracellular protozoan parasite that can form permanent cysts in the brain. Knowing that stress can increase the permeability of the blood-brain barrier, we hypothesized that stress could facilitate brain infection by TG, thus promoting the development of schizophrenia symptoms. The objective of this study was to test if different types of stress: acute stress (salivary cortisol), chronic stress (hair cortisol), or childhood adversity (Childhood Experiences of Violence Questionnaire), modulate the link between TG (TG antibodies in serum) and schizophrenia.

Method: Data and biospecimens (saliva, hair and serum) from 226 schizophrenic patients and 129 controls from the Signature Bank of the Centre de recherche de l’Institut Universitaire en Santé Mentale de Montréal were analysed. Hypothesis was tested using logistic regressions. Sex and age were included as covariates.

Results: Interaction effects revealed that the relation between TG seropositivity and the risk of developing schizophrenia was modulated by levels of hair cortisol (chronic stress; OR = 3.97, CI₉₅ = 1.01- 15.71, p=.049). However, salivary cortisol (acute stress; OR = 1.72, CI₉₅ = 0.60-4.95, p=.315) and childhood adversity (OR = 1.01, CI₉₅ = 0.85-1.19, p=.931) did not increase the risk of schizophrenia in TG infected patients.

Conclusion: These results provide a step towards a better understanding of the role of stress in the association between TG and schizophrenia.

Authors: Antoine M. Dujon, Justine Boutry, Sophie Tissot, Jordan Meliani, Anna Miltiadous, Jácint Tokolyi, Beata Ujvari, Frédéric Thomas

Source: Science of The Total Environment (Aug 2024)

Abstract

Tumoural processes, ubiquitous phenomena in multicellular organisms, influence evolutionary trajectories of all species. To gain a holistic understanding of their impact on species’ biology, suitable laboratory models are required. Such models are characterised by a widespread availability, ease of cultivation, and reproducible tumour induction. It is especially important to explore, through experimental approaches, how tumoural processes alter ecosystem functioning.

The cnidarian Hydra oligactis is currently emerging as a promising model due to its development of both transmissible and non-transmissible tumours and the wide breadth of experiments that can be conducted with this species (at the individual, population, mechanistic, and evolutionary levels). However, tumoural hydras are, so far, only documented in Europe, and it is not clear if the phenomenon is local or widespread.

In this study we demonstrate that Australian hydras from two independent river networks develop tumours in the laboratory consisting of interstitial stem cells and display phenotypic alterations (supernumerary tentacles) akin to European counterparts. This finding confirms the value of this model for ecological and evolutionary research on host-tumour interactions.

Authors: Mathieu Giraudeau, Orsolya Vincze, Sophie M. Dupont, Tuul Sepp, Ciara Baines, Jean-Francois Lemaitre, Karin Lemberger, Sophie Gentès, Amy Boddy, Antoine M. Dujon, Georgina Bramwell, Valerie Harris, Beata Ujvari, Catherine Alix-Panabières, Stephane Lair, David Sayag, Dalia A. Conde, Fernando Colchero, Tara M. Harrison, Samuel Pavard, Benjamin Padilla-Morales, Damien Chevallier, Rodrigo Hamede, Benjamin Roche, Tamas Malkocs, Athena C. Aktipis, Carlo Maley, James DeGregori, Guillaume Le Loc’h, Frédéric Thomas

Source: Journal of Animal Ecology (Aug 2024)

Abstract

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists.

Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine.

The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations.

Authors: Antoine M Dujon, Beata Ujvari, Sophie Tissot, Jordan Meliani, Océane Rieu, Nikita Stepanskyy, Rodrigo Hamede, Jácint Tokolyi, Aurora Nedelcu, Frédéric Thomas

Source: Evolutionary Applications (Aug 2024)

Abstract

Growing evidence indicates that human activities are causing cancer rates to rise in both human and wildlife populations. This is due to the inability of ancestral anti-cancer defences to cope with modern environmental risks. The evolutionary mismatch between modern oncogenic risks and evolved cancer defences has far-reaching effects on various biological aspects at different timeframes, demanding a comprehensive study of the biology and evolutionary ecology of the affected species.

Firstly, the increased activation of anti-cancer defences leads to excessive energy expenditure, affecting other biological functions and potentially causing health issues like autoimmune diseases. Secondly, tumorigenesis itself can impact important fitness-related parameters such as competitiveness, predator evasion, resistance to parasites, and dispersal capacity. Thirdly, rising cancer risks can influence the species’ life-history traits, often favoring early reproduction to offset fitness costs associated with cancer.

However, this strategy has its limits, and it may not ensure the sustainability of the species if cancer risks continue to rise. Lastly, some species may evolve additional anti-cancer defences, with uncertain consequences for their biology and future evolutionary path.

In summary, we argue that the effects of increased exposure to cancer-causing substances on wildlife are complex, ranging from immediate responses to long-term evolutionary changes. Understanding these processes, especially in the context of conservation biology, is urgently needed.

Authors: Nick MacDonald, Nynke Raven, Wendy Diep, Samantha Evans, Senuri Pannipitiya, Georgina Bramwell, Caitlin Vanbeek, Frédéric Thomas, Tracey Russell, Antoine M. Dujon, Marina Telonis-Scott & Beáta Újvári

Source: Scientific Reports (May 2024)

Abstract

Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected.

Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M).

This approach allowed us to conduct a fine scale analysis of gene wide and site-specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species’ evolution.

The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2’s status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site-specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site-specific selection analyses to understand the evolution of highly complex gene families.

Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.

Authors: Georgina Bramwell, James DeGregori, Frédéric Thomas, Beáta Újvári

Source: Evolution (Apr 2024)

Abstract

Evolutionary theory predicts that the accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e., transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules and survive for centuries and millennia.

The currently known 11 transmissible cancer lineages occur in dogs (canine venereal tumour disease), in Tasmanian devils (devil facial tumor diseases, DFT₁ and DFT₂), and in bivalves (bivalve transmissible neoplasia). Despite the mutation loads of these cell lines being much higher than observed in human cancers, they have not been eliminated in space and time.

Here, we provide potential explanations for how these fascinating cell lines may have overcome the fitness decline due to the progressive accumulation of deleterious mutations and propose that the high mutation load may carry an indirect positive fitness outcome.

We offer ideas on how these host–pathogen systems could be used to answer outstanding questions in evolutionary biology. The recent studies on the evolution of these clonal pathogens reveal key mechanistic insight into transmissible cancer genomes, information that is essential for future studies investigating how these contagious cancer cell lines can repeatedly evade immune recognition, evolve, and survive in the landscape of highly diverse hosts.