Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
| Autor: | Diego A. Golombek, Luciano Marpegan, Carlos S. Caldart, Carla V. Finkielstein, M. L. Mul Fedele, Natalia Paladino, F. Román, Juan José Chiesa, I. Aiello |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
tumor
medicine.medical_treatment Circadian clock Cell Immunology Biology Proinflammatory cytokine purl.org/becyt/ford/1 [https] 03 medical and health sciences Mice 0302 clinical medicine Immune system Circadian Clocks Neoplasms medicine Tumor Microenvironment Animals purl.org/becyt/ford/1.6 [https] skin and connective tissue diseases Research Articles 030304 developmental biology Cyclin Cancer Cell Proliferation 0303 health sciences Multidisciplinary Cell Cycle SciAdv r-articles Cell cycle biochemical phenomena metabolism and nutrition Cell biology Circadian Rhythm CLOCK Cytokine medicine.anatomical_structure circadian cell cycle sense organs immune 030217 neurology & neurosurgery Research Article |
| Zdroj: | Science Advances CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 2375-2548 |
| Popis: | Circadian disruption promotes tumor growth by changes in circadian rhythms of immune cells, clock genes, and cell cycle genes. Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1, all of which contribute to a proliferative phenotype. |
| Databáze: | OpenAIRE |
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