Next Article in Journal
Prenatal Metformin Therapy Attenuates Hypertension of Developmental Origin in Male Adult Offspring Exposed to Maternal High-Fructose and Post-Weaning High-Fat Diets
Next Article in Special Issue
Spatiotemporal Labeling of Melanocytes in Mice
Previous Article in Journal
In Vitro Influence of Extracts from Snail Helix aspersa Müller on the Colon Cancer Cell Line Caco-2
Previous Article in Special Issue
Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials
Open AccessArticle

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

1
Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-900, Brazil
2
Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-900, Brazil
3
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(4), 1065; https://doi.org/10.3390/ijms19041065
Received: 30 January 2018 / Revised: 27 March 2018 / Accepted: 29 March 2018 / Published: 3 April 2018
(This article belongs to the Special Issue Animal Models of Melanoma)
The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target. View Full-Text
Keywords: cancer; melanoma; tumor microenvironment; tumor macroenvironment; central and peripheral clocks; chronodisruption cancer; melanoma; tumor microenvironment; tumor macroenvironment; central and peripheral clocks; chronodisruption
Show Figures

Figure 1

MDPI and ACS Style

De Assis, L.V.M.; Moraes, M.N.; Magalhães-Marques, K.K.; Kinker, G.S.; Da Silveira Cruz-Machado, S.; De Lauro Castrucci, A.M. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks. Int. J. Mol. Sci. 2018, 19, 1065.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop