Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

Lupu,Mihai; Caruntu,Ana; Caruntu,Constantin; Papagheorghe,Laura Maria Lucia; Ilie,Mihaela Adriana; Voiculescu,Vlad; Boda,Daniel; Constantin,Carolina; Tanase,Cristiana; Sifaki,Maria; Drakoulis,Nikolaos; Mamoulakis,Charalampos; Tzanakakis,George; Neagu,Monica; Spandidos,Demetrios A.; Izotov,Boris N.; Tsatsakis,Aristides M.

doi:10.3892/or.2017.5817

Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

Authors:
- Mihai Lupu
- Ana Caruntu
- Constantin Caruntu
- Laura Maria Lucia Papagheorghe
- Mihaela Adriana Ilie
- Vlad Voiculescu
- Daniel Boda
- Carolina Constantin
- Cristiana Tanase
- Maria Sifaki
- Nikolaos Drakoulis
- Charalampos Mamoulakis
- George Tzanakakis
- Monica Neagu
- Demetrios A. Spandidos
- Boris N. Izotov
- Aristides M. Tsatsakis
View Affiliations

Affiliations: Department of Dermatology, MEDAS Medical Center, 030442 Bucharest, Romania, Department of Oral and Maxillofacial Surgery, ‘Carol Davila’ Central Military Emergency Hospital, 010825 Bucharest, Romania, Department of Physiology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Dermatology Ambulatory Center, ‘Colțea’ Clinical Hospital, 030171 Bucharest, Romania, Dermatology Research Laboratory, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Dermatology and Allergology, Elias Emergency University Hospital, 011461 Bucharest, Romania, ‘Victor Babes’ National Institute of Pathology, 050096 Bucharest, Romania, ‘Titu Maiorescu’ University, Faculty of Medicine, 031593 Bucharest, Romania, Laboratory of Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece, Department of Urology, University General Hospital of Heraklion, University of Crete Medical School, 71003 Heraklion, Greece, Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece, Department of Analytical Toxicology, Pharmaceutical Chemistry and Pharmacognosy, Sechenov University, 119991 Moscow, Russia
Published online on: July 13, 2017 https://doi.org/10.3892/or.2017.5817
Pages: 1327-1340
Copyright: © Lupu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun‑protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun‑exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. Aside from the well‑known etiopathogenic factors, studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with the exception of penile SCC, for which a paucity of specific data on their pathogenic role exists. The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene‑related peptide and somatostatin, as well as neurohormones, such as proopiomelanocortin and its derived peptides, α‑melanocyte‑stimulating hormone and adrenocorticotropin. All these factors have been, at least at some point, a subject of debate regarding their precise role in the pathogenesis of NMSC. There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC. Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. Further studies are required in order to elucidate the exact mechanisms through which neuroactive molecules promote or inhibit cutaneous carcinogenesis, as this could lead to the development of more sophisticated and tailored treatment protocols, as well as open new perspectives in skin cancer research.

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