Do malignant cells sleep at night?
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Do malignant cells sleep at night? Luis Enrique Cortés-Hernández1†, Zahra Eslami-S1†, Antoine M. Dujon2,3, Mathieu Giraudeau2, Beata Ujvari3,4, Frédéric Thomas2† and Catherine Alix-Panabières1,2,5*† * Correspondence: c-panabieres@ chu-montpellier.fr † Luis Enrique Cortés-Hernández, Zahra Eslami-S, Frédéric Thomas and Catherine Alix-Panabières contributed equally to this work. 1 Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, Montpellier, France 2 CREEC (CREES), Unité Mixte de Recherches, IRD 224–CNRS 5290– Université de Montpellier, Montpellier, France Full list of author information is available at the end of the article
Abstract Biological rhythms regulate the biology of most, if not all living creatures, from whole organisms to their constitutive cells, their microbiota, and also parasites. Here, we present the hypothesis that internal and external ecological variations induced by biological cycles also influence or are exploited by cancer cells, especially by circulating tumor cells, the key players in the metastatic cascade. We then discuss the possible clinical implications of the effect of biological cycles on cancer progression, and how they could be exploited to improve and standardize methods used in the liquid biopsy field. Keywords: Circadian cycle, Tumor dissemination, Circulating tumor cells, Chronobiology, Phenology, Disease ecology
Introduction Since the early 1940s, multicellular organisms are no longer considered autonomous entities, but rather “holobionts,” i.e., assemblages composed of the host and its associated commensal and mutualistic microorganisms and parasitic taxa [1, 2]. Recently, Thomas et al. [3] proposed that multicellular organisms have a long evolutionary history with a third category of living entities inside their bodies: cancer cell communities (oncobiota). From precancerous lesions to metastatic cancers, oncogenic processes are very frequent in humans and animals [4, 5], and not just during aging as often thought in the past [6]. From an evolutionary perspective, the transformation of normal cells into malignant cells that will form a cancer is equivalent to a speciation event inside the body [7, 8], preceded by a set of mutations that allow normal cells to acquire selfdefined fitness functions and on which natural selection can act [9]. As the holobiont components are usually prisoners of their host, their environment is composed of at least two very different ecological dimensions: the host (i.e., the immediate environment) and the host habitat (i.e., the ecosystem). The first type of environmental variables that holobiont members experience are the host physiological, genetic, and phenotypic characteristics, such as sex, age, and immunocompetence. The second level of environmental variability is due to the biotic and abiotic factors that characterize the ecosystem in which the host lives (resource level, abundance of predators, seasons). These intra- and inter-individual © The Author(s). 2020 Open Access This
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