Cancer and mosquitoes – An unsuspected close connection

Authors: Audrey Arnal, Benjamin Roche, Louis-Clément Gouagna, Antoine Dujon, Beata Ujvari, et al.

Source: Science of The Total Environment (JUN 2020)

Graphical abstract:

Brief summary of the paper:

Cancer is a major public health issue and represents a significant burden in countries with different levels of economic wealth. In parallel, mosquito-borne infectious diseases represent a growing problem causing significant morbidity and mortality worldwide.

Acknowledging that these two concerns are both globally distributed, it is essential to investigate whether they have a reciprocal connection that can fuel their respective burdens. Unfortunately, very few studies have examined the link between these two threats.

This review provides an overview of the possible links between mosquitoes, mosquito-borne infectious diseases and cancer.

We first focus on the impact of mosquitoes on carcinogenesis in humans including the transmission of oncogenic pathogens through mosquitoes, the immune reactions following mosquito bites, the presence of non-oncogenic mosquito-borne pathogens, and the direct transmission of cancer cells.

The second part of this review deals with the direct or indirect consequences of cancer in humans on mosquito behaviour.

Thirdly, we discuss the potential impacts that natural cancers in mosquitoes can have on their life history traits and therefore on their vector capacity. Finally, we discuss the most promising research avenues on this topic and the integrative public health strategies that could be envisioned in this context.

Predation shapes the impact of cancer on population dynamics and the evolution of cancer resistance

Authors: Cédric Perret; Cindy Gidoin; Beata Ujvari; Frédéric Thomas & Benjamin Roche

Source: EVOLUTIONARY APPLICATIONS (June 2020)

Brief summary of the paper:

Cancer is a widespread disease that affects most of the metazoans. However, cancer development is a slow process and, long before causing the death of the individual, may weaken organisms’ capacities and impair their interactions with other species.

Yet, the impact of cancer development on biotic interactions, and over the dynamics of the whole ecosystem, is still largely unexplored. As well, the feedback of altered biotic interactions on the evolution of resistance against cancer in the context of community ecology has not been investigated.

From this new perspective, we theoretically investigate how cancer can challenge expected interaction outcomes in a predator–prey model system, and how, in return, these altered interaction outcomes could affect evolution of resistance mechanism against cancer.

First, we demonstrate a clear difference between prey and predator vulnerability to cancer, with cancer having a limited impact on prey populations. Second, we show that biotic interactions can surprisingly lead to a null or positive effect of cancer on population densities.

Finally, our evolutionary analysis sheds light on how biotic interactions can lead to diverse resistance levels in predator populations. While its role in ecosystems is mostly unknown, we demonstrate that cancer in wildlife is an important ecological and evolutionary force to consider.

The interface between ecology, evolution, and cancer: More than ever a relevant research direction for both oncologists and ecologists

Authors: Frédéric Thomas; Benjamin Roche; Mathieu Giraudeau; Rodrigo Hamede & Beata Ujvari

Source: EVOLUTIONARY APPLICATIONS (June 2020)

Brief summary of the paper:

Forty years ago, scientists started to describe the genetic cascade of events leading to cancer as “somatic evolution”. Even if the full relevance of these pioneer papers was not immediately perceived by the scientific community, they paved the way for one of the most stimulating and challenging research directions in the effort to predict cancer emergence, progression, and therapy outcomes.

Evolutionary biology has indeed deeply transformed our understanding of cancer, gaining unprecedented international recognition among oncologists in the last decade. Nowadays, cancer is widely considered as a pathology that emerges due to clonal evolution and cell competition, Darwinian selection being the driver of cancer cells along selective landscapes, culminating in resistance to immune attack, malignant progression, resistance to therapies, metastasis, and even sometimes contagion between individuals and/or species. Thus, as recently proposed by Mel Greaves through paraphrasing Dobzhansky’s famous dictum, “nothing in cancer makes sense except in the light of evolution”.

This interdisciplinary field of research remains at the moment extremely promising, but it is still in its infancy, and fundamental studies (both theoretical and experimental) are still needed to pursue our understanding of the evolutionary ecology of tumors and of host–tumor interactions.

By assembling some of the latest, most exciting results, syntheses, and perspectives relating to the topic Ecology, Evolution and Cancer, our objective with this special issue is to reinforce the construction of a solid base for a balanced approach to cancer research, for oncologists and for ecologists.

Can Energetic Capacity Help Explain Why Physical Activity Reduces Cancer Risk?

Authors: Peter A. Biro; FrédéricThomas; Beata Ujvari; Christa Beckmann

Source: Trends in Cancer (June 2020)

Brief summary of the paper:

Physical activity substantially reduces the risk of developing cancer. As such, exercise promises to be a powerful preventative measure against cancer.

However, if we are to ‘prescribe’ exercise, we should identify how and why exercise affects cancer risk to provide informed prescriptions.

We find that high energetic capacity is both a cause and consequence of high sustained activity levels, both at a genetic level and due to training effects.

High energetic capacity in turn can increase immune responses and reduce incidence and progression of cancer, and this effect can be independent of activity. Thus, exercise may reduce cancer risk via increasing one’s energetic capacity for immune function.

In light of this potential mechanism, prescriptions for exercise might consider those likely to increase one’s energetic capacity, which may differ among individuals given innate differences in our ability to generate energy on a sustained basis.

Increased physical activity reduces cancer risk in humans, but why this whole-organism attribute reduces cancer remains unclear. Active individuals tend to have high capacity to generate energy on a sustained basis, which in turn can permit greater immune responses crucial for fighting emerging neoplasia.

Thus, we suggest energetic capacity as a potential mechanism to explain the activity–cancer link, given that humans are intrinsically (not externally) energy limited.

Human and rodent studies show that individuals with high energetic capacity mount greater immune responses and have lower cancer incidence; these trends persist after controlling for actual physical activity, supporting a direct role of energetic capacity.

If true, exercise efforts might best target those that increase one’s energetic capacity, which may be both individual and exercise specific.

Transmissible Cancers in an Evolutionary Perspective

Authors: Antoine M. Dujon, Robert A. Gatenby, Georgina Bramwell, Nick MacDonald, Erin Dohrmann, Nynke Raven, Aaron Schultz, Rodrigo Hamede, Anne-Lise Gérard, Mathieu Giraudeau, Frédéric Thomas & Beata Ujvari

Source: iScience (June 2020)

Brief summary of the paper:

Graphical Abstract:

Inter-individual transmission of cancer cells represents an intriguing and unexplored host-pathogen system, with significant ecological and evolutionary ramifications. The pathogen consists of clonal malignant cell lines that spread horizontally as allografts and/or xenografts.

Although only nine transmissible cancer lineages in eight host species from both terrestrial and marine environments have been investigated, they exhibit evolutionary dynamics that may provide novel insights into tumor-host interactions particularly in the formation of metastases.

Here we present an overview of known transmissible cancers, discuss the necessary and sufficient conditions for cancer transmission, and provide a comprehensive review on the evolutionary dynamics between transmissible cancers and their hosts.

Demography and spatial requirements of the endangered northern quoll on Groote Eylandt

Authors: Jaime Heiniger, Skye F. Cameron, Thomas Madsen, Amanda C. Niehaus and Robbie S. Wilson

Source: Wildlife Research (May 2020)

Pic by: Wildlife Explorer / CC BY (https://creativecommons.org/licenses/by/3.0)

Brief summary of the paper:

Context: Australia has experienced the highest number of mammal extinctions of any continent over the past two centuries. Understanding the demography and spatial requirements of populations before declines occur is fundamental to confirm species trajectory, elucidate causes of decline and develop effective management strategies.

Aims: We evaluated the demography and spatial requirements of a northern quoll, Dasyurus hallucatus, population on Groote Eylandt, Northern Territory. Groote Eylandt is considered a refuge for the species because key threatening processes are absent or limited; cane toads and introduced ungulates are absent, feral cats are infrequently detected and the fire regime is benign compared with mainland Northern Territory.

Methods: We conducted a 4-year capture–mark–recapture study to monitor growth, reproduction and survival of northern quolls within a 128-ha area, and we evaluated spatial requirements by attaching GPS units to both sexes. To assess the status of the Groote Eylandt population, we compared the demographics with existing data from mainland populations.

Key results: The average density of northern quolls was 0.33 ha¯¹. However, there was a 58% decline in female density, primarily between 2012 and 2013, corresponding with a decrease in female body mass. Females survived and bred in up to 3 years and adult survival rates did not vary among years, suggesting that juvenile recruitment drives population fluctuations. Male quolls were semelparous, with die-off occurring in the months following breeding. The median female and male home ranges were 15.7 ha and 128.6 ha respectively, and male ranges increased significantly during breeding, with 1616 ha being the largest recorded.

Conclusions: The northern quoll population on Groote Eylandt had a higher density, female survival and reproductive success than has been previously recorded on the mainland. However, a marked decline was recorded corresponding with a decrease in female mass, indicating below-average rainfall as the likely cause.

Implications: Groote Eylandt remains a refuge for the endangered northern quoll. However, even in the absence of key threatening processes, the population has declined markedly, highlighting the impact of environmental fluctuations. Maintaining the ecological integrity of Groote Eylandt is imperative for population recovery, and managing threats on the mainland over appropriate spatial scales is necessary to increase population resilience.

High numbers of unrelated reproductives in the Australian ‘higher’ termite Nasutitermes exitiosus (Blattodea: Termitidae)

Authors: Montagu, A.; Lee, T. R. C.; Ujvari, B; et al.

Source: INSECTES SOCIAUX

Pic by: Forestry and Forest Products

Brief summary of the paper:

Social insect colonies are among the most complex social organisations in nature, with reproductive and non-reproductive individuals co-ordinating to maintain the survival of the colony.

Multiple reproductive schemes occur in social insects, from simple schemes with one founding reproductive pair, to more complex ones involving within-colony inbreeding and more than two unrelated reproductives.

Colony breeding schemes and genetic structure remain understudied in termites, compared to the Hymenoptera. In this study, we performed the first genetic characterisation of the colony breeding structure of Nasutitermes exitiosus (Blattodea: Termitidae), an endemic Australian termite with a broad distribution across southern mainland Australia.

We analysed the genetic structure of 60 N. exitiosus colonies from the Eastern part of its distribution, using microsatellites and mitochondrial sequence data. We found that most colonies were headed by one founding pair of reproductives, although some colonies exhibited a more complex breeding structure, including within-colony inbreeding and the presence of multiple unrelated reproductives.

We found evidence for the presence of seven unrelated queens in one colony, to our knowledge, the highest number of unrelated queens yet found in a termite from the family Termitidae. We found some evidence for genetic isolation by distance, indicating that the species is a relatively poor disperser over long ranges.

The evolution of resistance and tolerance as cancer defences

Authors: Thomas, Frederic; Giraudeau, Mathieu; Gouzerh, Flora; Boutry, Justine; Renaud, Francois; Pujol, Pascal; Tasiemski, Aurelie; Bernex, Florence; Maraver, Antonio; Bousquet, Emilie; Dormont, Laurent; Osterkamp, Jens; Roche, Benjamin; Hamede, Rodrigo; Ujvari, Beata.

Source: PARASITOLOGY

Brief summary of the paper:

Although there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation.

The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option ‘tolerance’ to cancer.

Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer.

Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival.

Will urbanisation affect the expression level of genes related to cancer of wild great tits?

Authors: Giraudeau, Mathieu; Watson, Hannah; Powell, Daniel; Vincze, Orsolya; Thomas, Frederic; Sepp, Tuul; Ujvari, Beata; et al.

Source: SCIENCE OF THE TOTAL ENVIRONMENT

Brief summary of the paper:

Recent studies suggest that oncogenic processes (from precancerous lesions to metastatic cancers) are widespread in wild animal species, but their importance for ecosystem functioning is still underestimated by evolutionary biologists and animal ecologists.

Similar to what has been observed in humans, environmental modifications that often place wild organisms into an evolutionary trap and/or exposes them to a cocktail of mutagenic and carcinogenic pollutants might favor cancer emergence and progression, if animals do not up-regulate their defenses against these pathologies.

Here, we compared, for the first time, the expression of 59 tumor-suppressor genes in blood and liver tissues of urban and rural great tits (Parus major); urban conditions being known to favor cancer progression due to, among other things, exposure to chemical or light pollution.

Contrary to earlier indications, once we aligned the transcriptome to the great tit genome, we found negligible differences in the expression of anti-cancer defenses between urban and rural birds in blood and liver. Our results indicate the higher expression of a single caretaker gene (i.e. BRCA1) in livers of rural compared to urban birds.

We conclude that, while urban birds might be exposed to an environment favoring the development of oncogenic processes, they seem to not upregulate their cancer defenses accordingly and future studies should confirm this result by assessing more markers of cancer defenses.

This may result in a mismatch that might predispose urban birds to higher cancer risk and future studies in urban ecology should take into account this, so far completely ignored, hazard.

Differences in mutational processes and intra-tumour heterogeneity between organs: The local selective filter hypothesis

Authors: Giraudeau, Mathieu; Sepp, Tuul; Ujvari, Beata; et al.

Source: EVOLUTION MEDICINE AND PUBLIC HEALTH

Brief summary of the paper:

Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment.

We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs’ theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms.

Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours.

When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences.

In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis.

Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.