Conséquences écologiques, évolutives et appliquées des modifications d'odeurs corporelles associées au cancer .

In many animal species, chemical communication plays a major role in interactions between individuals, both at the intraspecific and interspecific levels (sexual selection, competition, predation, etc.). Although it is known that many pathologies are associated with changes in body odour, little work has been done on the ecological and evolutionary consequences of these phenomena. Moreover, most research on this subject concerns infectious diseases, suggesting for example an avoidance of contagion between individuals, but much more rarely cancers. This thesis aims to better understand how cancer processes (from pre-cancerous lesions to metastatic cancers) influence interactions between individuals through the changes in body odour that they cause. To conduct our research, we used a biological host/cancer model: the mouse/lung cancer. In addition to clarifying the role of cancer-associated odours in inter-organism interactions, this research project also aimed to identify the stage of cancer development at which olfactory changes are observable, with the applied objective of identifying possible early cancer biomarkers of medical relevance. On the applied side, we were able to observe odour changes very early in the development of the disease, from the onset of precancerous lesions, and several potential biomarker compounds were identified. Our results thus indicate that lung cancer in mice alters body odours early on, and that these can be detected both by chemical analysis and by using healthy mice as noses. These findings open up new research perspectives in the medical field. Regarding the impact of cancer on the behaviour of healthy conspecifics, our results suggest that the disease does not seem to play a role in the preferences of female mice, contrary to what is generally observed in the context of parasitism. This new field of study, which brings together chemical ecology and cancer, is only just beginning and many questions remain to be answered, particularly with regard to other interactions such as prey-predator, or in the case of transmissible cancers such as in the Tasmanian devil. This thesis opens up numerous research perspectives, both in the medical field and in fundamental biology.Chez de nombreuses espèces animales, la communication chimique joue un rôle majeur dans les interactions entre individus, tant au niveau intraspécifique qu'interspécifique (sélection sexuelle, compétition, prédation, etc.). S'il est établi que bon nombre de pathologies sont associées à des modifications d’odeurs corporelles, peu de travaux ont été consacrés aux conséquences écologiques et évolutives de ces phénomènes. De plus, la plupart des recherches sur ce sujet concernent les maladies infectieuses, suggérant par exemple un évitement de la contagion entre individus, mais beaucoup plus rarement les cancers. Cette thèse vise à mieux comprendre comment les processus cancéreux (des lésions précancéreuses aux cancers métastatiques) influencent les interactions entre individus au travers des modifications d’odeurs corporelles qu'ils entraînent. Pour mener nos recherches, nous avons utilisé un modèle biologique hôte/cancer : la souris/cancer du poumon. En plus de clarifier le rôle des odeurs associées au cancer dans les interactions entre organismes, ce projet de recherche visait également à identifier le stade de développement du cancer à partir duquel les changements olfactifs sont observables, avec l’objectif appliqué de mettre en évidence de possibles biomarqueurs précoces du cancer présentant un intérêt médical. Concernant l'aspect appliqué, nous avons pu observer des modifications d'odeurs très tôt dans le développement de la maladie, dès l'apparition des lésions précancéreuses, et plusieurs composés biomarqueurs potentiels ont été identifiés. Nos résultats indiquent ainsi que le cancer du poumon chez la souris modifie de manière précoce les odeurs corporelles, et que celles-ci peuvent être détectées aussi bien par des analyses chimiques que par l’utilisation de souris saines comme nez. Ces conclusions ouvrent des perspectives de recherche dans le domaine médical. Concernant l’impact du cancer sur le comportement des congénères sains, nos résultats suggèrent que la maladie ne semble pas jouer de rôle sur les préférences des souris femelles, contrairement à ce qui est généralement observé dans le cadre du parasitisme. Ce nouveau domaine d’étude, qui réunit l’écologie chimique et le cancer, ne fait que démarrer et de nombreuses questions restent à élucider, notamment vis-à-vis d’autres interactions telles que proie-prédateur, ou encore dans le cas des cancers transmissibles comme chez le diable de Tasmanie. Cette thèse ouvre de nombreuses perspectives de recherche, tant sur le plan médical que sur le plan de la biologie fondamentale

Ecological, evolutionary and applied consequences of changes in body odor associated with cancer.

Chez de nombreuses espèces animales, la communication chimique joue un rôle majeur dans les interactions entre individus, tant au niveau intraspécifique qu'interspécifique (sélection sexuelle, compétition, prédation, etc.). S'il est établi que bon nombre de pathologies sont associées à des modifications d’odeurs corporelles, peu de travaux ont été consacrés aux conséquences écologiques et évolutives de ces phénomènes. De plus, la plupart des recherches sur ce sujet concernent les maladies infectieuses, suggérant par exemple un évitement de la contagion entre individus, mais beaucoup plus rarement les cancers. Cette thèse vise à mieux comprendre comment les processus cancéreux (des lésions précancéreuses aux cancers métastatiques) influencent les interactions entre individus au travers des modifications d’odeurs corporelles qu'ils entraînent. Pour mener nos recherches, nous avons utilisé un modèle biologique hôte/cancer : la souris/cancer du poumon. En plus de clarifier le rôle des odeurs associées au cancer dans les interactions entre organismes, ce projet de recherche visait également à identifier le stade de développement du cancer à partir duquel les changements olfactifs sont observables, avec l’objectif appliqué de mettre en évidence de possibles biomarqueurs précoces du cancer présentant un intérêt médical. Concernant l'aspect appliqué, nous avons pu observer des modifications d'odeurs très tôt dans le développement de la maladie, dès l'apparition des lésions précancéreuses, et plusieurs composés biomarqueurs potentiels ont été identifiés. Nos résultats indiquent ainsi que le cancer du poumon chez la souris modifie de manière précoce les odeurs corporelles, et que celles-ci peuvent être détectées aussi bien par des analyses chimiques que par l’utilisation de souris saines comme nez. Ces conclusions ouvrent des perspectives de recherche dans le domaine médical. Concernant l’impact du cancer sur le comportement des congénères sains, nos résultats suggèrent que la maladie ne semble pas jouer de rôle sur les préférences des souris femelles, contrairement à ce qui est généralement observé dans le cadre du parasitisme. Ce nouveau domaine d’étude, qui réunit l’écologie chimique et le cancer, ne fait que démarrer et de nombreuses questions restent à élucider, notamment vis-à-vis d’autres interactions telles que proie-prédateur, ou encore dans le cas des cancers transmissibles comme chez le diable de Tasmanie. Cette thèse ouvre de nombreuses perspectives de recherche, tant sur le plan médical que sur le plan de la biologie fondamentale.In many animal species, chemical communication plays a major role in interactions between individuals, both at the intraspecific and interspecific levels (sexual selection, competition, predation, etc.). Although it is known that many pathologies are associated with changes in body odour, little work has been done on the ecological and evolutionary consequences of these phenomena. Moreover, most research on this subject concerns infectious diseases, suggesting for example an avoidance of contagion between individuals, but much more rarely cancers. This thesis aims to better understand how cancer processes (from pre-cancerous lesions to metastatic cancers) influence interactions between individuals through the changes in body odour that they cause. To conduct our research, we used a biological host/cancer model: the mouse/lung cancer. In addition to clarifying the role of cancer-associated odours in inter-organism interactions, this research project also aimed to identify the stage of cancer development at which olfactory changes are observable, with the applied objective of identifying possible early cancer biomarkers of medical relevance. On the applied side, we were able to observe odour changes very early in the development of the disease, from the onset of precancerous lesions, and several potential biomarker compounds were identified. Our results thus indicate that lung cancer in mice alters body odours early on, and that these can be detected both by chemical analysis and by using healthy mice as noses. These findings open up new research perspectives in the medical field. Regarding the impact of cancer on the behaviour of healthy conspecifics, our results suggest that the disease does not seem to play a role in the preferences of female mice, contrary to what is generally observed in the context of parasitism. This new field of study, which brings together chemical ecology and cancer, is only just beginning and many questions remain to be answered, particularly with regard to other interactions such as prey-predator, or in the case of transmissible cancers such as in the Tasmanian devil. This thesis opens up numerous research perspectives, both in the medical field and in fundamental biology

Conséquences écologiques, évolutives et appliquées des modifications d'odeurs corporelles associées au cancer .

In many animal species, chemical communication plays a major role in interactions between individuals, both at the intraspecific and interspecific levels (sexual selection, competition, predation, etc.). Although it is known that many pathologies are associated with changes in body odour, little work has been done on the ecological and evolutionary consequences of these phenomena. Moreover, most research on this subject concerns infectious diseases, suggesting for example an avoidance of contagion between individuals, but much more rarely cancers. This thesis aims to better understand how cancer processes (from pre-cancerous lesions to metastatic cancers) influence interactions between individuals through the changes in body odour that they cause. To conduct our research, we used a biological host/cancer model: the mouse/lung cancer. In addition to clarifying the role of cancer-associated odours in inter-organism interactions, this research project also aimed to identify the stage of cancer development at which olfactory changes are observable, with the applied objective of identifying possible early cancer biomarkers of medical relevance. On the applied side, we were able to observe odour changes very early in the development of the disease, from the onset of precancerous lesions, and several potential biomarker compounds were identified. Our results thus indicate that lung cancer in mice alters body odours early on, and that these can be detected both by chemical analysis and by using healthy mice as noses. These findings open up new research perspectives in the medical field. Regarding the impact of cancer on the behaviour of healthy conspecifics, our results suggest that the disease does not seem to play a role in the preferences of female mice, contrary to what is generally observed in the context of parasitism. This new field of study, which brings together chemical ecology and cancer, is only just beginning and many questions remain to be answered, particularly with regard to other interactions such as prey-predator, or in the case of transmissible cancers such as in the Tasmanian devil. This thesis opens up numerous research perspectives, both in the medical field and in fundamental biology.Chez de nombreuses espèces animales, la communication chimique joue un rôle majeur dans les interactions entre individus, tant au niveau intraspécifique qu'interspécifique (sélection sexuelle, compétition, prédation, etc.). S'il est établi que bon nombre de pathologies sont associées à des modifications d’odeurs corporelles, peu de travaux ont été consacrés aux conséquences écologiques et évolutives de ces phénomènes. De plus, la plupart des recherches sur ce sujet concernent les maladies infectieuses, suggérant par exemple un évitement de la contagion entre individus, mais beaucoup plus rarement les cancers. Cette thèse vise à mieux comprendre comment les processus cancéreux (des lésions précancéreuses aux cancers métastatiques) influencent les interactions entre individus au travers des modifications d’odeurs corporelles qu'ils entraînent. Pour mener nos recherches, nous avons utilisé un modèle biologique hôte/cancer : la souris/cancer du poumon. En plus de clarifier le rôle des odeurs associées au cancer dans les interactions entre organismes, ce projet de recherche visait également à identifier le stade de développement du cancer à partir duquel les changements olfactifs sont observables, avec l’objectif appliqué de mettre en évidence de possibles biomarqueurs précoces du cancer présentant un intérêt médical. Concernant l'aspect appliqué, nous avons pu observer des modifications d'odeurs très tôt dans le développement de la maladie, dès l'apparition des lésions précancéreuses, et plusieurs composés biomarqueurs potentiels ont été identifiés. Nos résultats indiquent ainsi que le cancer du poumon chez la souris modifie de manière précoce les odeurs corporelles, et que celles-ci peuvent être détectées aussi bien par des analyses chimiques que par l’utilisation de souris saines comme nez. Ces conclusions ouvrent des perspectives de recherche dans le domaine médical. Concernant l’impact du cancer sur le comportement des congénères sains, nos résultats suggèrent que la maladie ne semble pas jouer de rôle sur les préférences des souris femelles, contrairement à ce qui est généralement observé dans le cadre du parasitisme. Ce nouveau domaine d’étude, qui réunit l’écologie chimique et le cancer, ne fait que démarrer et de nombreuses questions restent à élucider, notamment vis-à-vis d’autres interactions telles que proie-prédateur, ou encore dans le cas des cancers transmissibles comme chez le diable de Tasmanie. Cette thèse ouvre de nombreuses perspectives de recherche, tant sur le plan médical que sur le plan de la biologie fondamentale

Ability of animals to detect cancer odors

The olfactory capacity of animals has long been used by humans to help with various activities, e.g., hunting, detecting mines, locating people, and diagnosing diseases. Cancer is among the leading diseases causing death worldwide. Several recent studies have underscored the benefit of using scent to detect cancer, and this paper will review the studies using animals to detect tumor scents. A large variety of animals have been used for this purpose-dogs, rodents, insects, and nematodes-and have shown their capacity to detect cancer, with a success rate close to 90%. Here we discuss these studies, their methodologies, and the animal models used. Finally, we discuss the medical perspectives for cancer diagnosis using odors

Odors and cancer: Current status and future directions

International audienceCancer is the second leading cause of death in the world. Because tumors detected at early stages are easier to treat, the search for biomarkers-especially non-invasive ones-that allow early detection of malignancies remains a central goal to reduce cancer mortality. Cancer, like other pathologies, often alters body odors, and much has been done by scientists over the last few decades to assess the value of volatile organic compounds (VOCs) as signatures of cancers. We present here a quantitative review of 208 studies carried out between 1984 and 2020 that explore VOCs as potential biomarkers of cancers. We analyzed the main findings of these studies, listing and classifying VOCs related to different cancer types while considering both sampling methods and analysis techniques. Considering this synthesis, we discuss several of the challenges and the most promising prospects of this research direction in the war against cancer

Detection of Volatile Organic Compounds from Preclinical Lung Cancer Mouse Models

International audienceVolatile organic compounds (VOCs) may help detect cancer tumour. This study addressed this question, as well as two methodological issues: 1) repeatability, comparing VOCs profiles obtained with two Solid Phase Micro Extraction (SPME) fibers used simultaneously; 2) detectability of cancer VOCs biomarkers, comparing profiles obtained following 1h versus 24h exposure of SPME fibers. We analyzed VOCs composition of soiled bedding obtained from a lung adenocarcinoma mouse model in which cancer was induced by doxycycline ingestion. We compared the VOCs profile of soiled bedding of cancerous (CC) and non-cancerous (NC) mice, before (T0), after two-weeks (T2) and after twelve weeks (T12) doxycycline ingestion. The results indicate: 1) qualitative and quantitative consistency in VOCs detection by two distinct SPME fibers ; 2) although more VOCs were detected following a 24h compared to 1h SPME exposure, none of the former molecules were related to cancer; 3) doxycycline impacted VOCs emissions in both CC and NC mice; 4) cancer impacted four VOCs at T12 only: the benzaldehyde which showed higher levels in CC mice and the hexan-1-ol and two mice pheromones, the 2 sec -butyl-4,5-dihydrothiazole and the 3,4-dehydro- exo -brevicomine, which showed lower levels in CC mice. Our study points out that the use of two SPME fibers and an extraction duration of 1h may be considered a good compromise allowing detection of cancer biomarkers while easing bench constraints

Odours of cancerous mouse congeners: detection and attractiveness

International audienceABSTRACT Chemical communication plays a major role in social interactions. Cancer, by inducing changes in body odours, may alter interactions between individuals. In the framework of research targeting non-invasive methods to detect early stages of cancer development, this study asked whether untrained mice could detect odour changes in cancerous congeners. If yes, were they able to detect cancer at an early developmental stage? Did it influence female preference? Did variations in volatile organic components of the odour source paralleled mice behavioural responses? We used transgenic mice strains developing or not lung cancer upon antibiotic ingestion. We sampled soiled bedding of cancerous mice (CC) and not cancerous mice (NC), at three experimental conditions: before (T0), early stage (T2) and late stage (T12) of cancer development. Habituation/generalisation and two-way preference tests were performed where soiled beddings of CC and NC mice were presented to wild-derived mice. The composition and relative concentration of volatile organic components (VOC) in the two stimuli types were analysed. Females did not show directional preference at any of the experimental conditions, suggesting that cancer did not influence their choice behaviour. Males did not discriminate between CC and NC stimuli at T0 but did so at T2 and T12, indicating that wild-derived mice could detect cancer at an early stage of development. Finally, although the VOC bouquet differed between CC and NC it did not seem to parallel the observed behavioural response suggesting that other types of odorant components might be involved in behavioural discrimination between CC and NC mice

Chemical signal is in the blend: bases of plant-pollinator encounter in a highly specialized interaction

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Urinary VOCs as biomarkers of early stage lung tumour development in mice

Background: Lung cancer is the primary cause of cancer-induced death. In addition to prevention and improved treatment, it has increasingly been established that early detection is critical to successful remission. Objective: The aim of this study was to identify volatile organic compounds (VOCs) in urine that could help diagnose mouse lung cancer at an early stage of its development. Methods: We analysed the VOC composition of urine in a genetically engineered lung adenocarcinoma mouse model with oncogenic EGFR doxycycline-inducible lung-specific expression. We compared the urinary VOCs of 10 cancerous mice and 10 healthy mice (controls) before and after doxycycline induction, every two weeks for 12 weeks, until full-blown carcinomas appeared. We used SPME fibres and gas chromatographymass spectrometry to detect variations in cancer-related urinary VOCs over time. Results: This study allowed us to identify eight diagnostic biomarkers that help discriminate early stages of cancer tumour development (i.e., before MRI imaging techniques could identify it). Conclusion: The analysis of mice urinary VOCs have shown that cancer can induce changes in odour profiles at an early stage of cancer development, opening a promising avenue for early diagnosis of lung cancer in other models

Rare and unique adaptations to cancer in domesticated species : an untapped resource?

Strong and ongoing artificial selection in domestic animals has resulted in amazing phenotypic responses that benefit humans, but often at a cost to an animal's health, and problems related to inbreeding depression, including a higher incidence of cancer. Despite high rates of cancer in domesticated species, little attention has been devoted to exploring the hypothesis that persistent artificial selection may also favour the evolution of compensatory anticancer defences. Indeed, there is evidence for effective anti-cancer defences found in several domesticated species associated with different cancer types. We also suggest that artificial selection can favour the “domestication” of inherited oncogenic mutations in rare instances, retaining those associated to late and/or less aggressive cancers, and that by studying these seemingly rare anticancer adaptations, novel cancer treatments may be found