- Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. Although melatonin is best known to regulate circadian rhythmicity and lower vertebrate skin pigmentation, the full spectrum of functional activities of this free radical-scavenging molecule, which also induces/promotes complex antioxidative and DNA repair systems, includes immunomodulatory, thermoregulatory, and antitumor properties. Because this plethora of functional melatonin properties still awaits to be fully appreciated by dermatologists, the current review synthesizes the main features that render melatonin a promising candidate for the management of several dermatoses associated with substantial oxidative damage.
- Extracellular vesicles (exosomes, microvesicles, and apoptotic bodies) are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell origin. Here, we review concepts in extracellular vesicle biology, with a focus on exosomes, highlighting recent studies in the field of dermatology.
- Conventional, static analyses have historically been the bedrock and tool of choice for the study of skin cancers. Over the past several years, in vivo imaging of tumors using multiphoton microscopy has emerged as a powerful preclinical tool for revealing detailed cellular behaviors from the earliest moments of tumor development to the final steps of metastasis. Multiphoton microscopy allows for deep tissue penetration with relatively minor phototoxicity, rendering it an effective tool for the long-term observation of tumor evolution.
- Cancer stem cells (CSCs) are found in many cancer types, including squamous cell carcinoma (SCC). CSCs initiate cancer formation and are linked to metastasis and resistance to therapies. Studies have revealed that several distinct CSC populations coexist in SCC and that tumor initiation and metastatic potential of these populations can be uncoupled. Therefore, it is critical to understand CSC biology to develop novel CSC-targeted therapies for patients with SCC with poor prognoses. This review compares the properties of CSCs in SCC with normal stem cells in the skin, summarizes current advances and characteristics of CSCs, and considers the challenges for CSC-targeted treatment of SCC.
- Cellular senescence, a state of stable cell cycle arrest in response to cellular stress, is an indispensable mechanism to counter tumorigenesis by halting the proliferation of damaged cells. However, through the secretion of an array of diverse cytokines, chemokines, growth factors, and proteases known as the senescence-associated secretory phenotype (SASP), senescent cells can paradoxically promote carcinogenesis. Consistent with this, removal of senescent cells delays the onset of cancer and prolongs lifespan in vivo, potentially in part through SASP reduction.
- Next-generation sequencing of melanomas has unraveled critical driver genes and genomic abnormalities, mostly defined as occurring at high frequency. In addition, less abundant mutations are present that link melanoma to a set of disorders, commonly called RASopathies. These disorders, which include neurofibromatosis and Noonan and Legius syndromes, harbor germline mutations in various RAS/mitogen-activated protein kinase signaling pathway genes. We highlight shared amino acid substitutions between this set of RASopathy mutations and those observed in large-scale melanoma sequencing data, uncovering a significant overlap.
- Angiotropism in melanoma correlates with ulceration and poor prognosis. It has been shown to be a marker of pericytic mimicry, that is, the spreading of tumor cells in a pericyte location along abluminal vascular surfaces. Such extravascular tumor spread may represent another form of tumor plasticity with reversion to a neural crest cell migratory phenotype. In a murine melanoma model, it has recently been demonstrated that neutrophilic skin inflammation promotes angiotropism and metastatic spread of primary melanomas.