Snapshot – changing melanocyte identity in melanoma developing route

Abstract

The largest organ with immune function, the skin, has complex structure and various physiological functions. Cells comprising this complex structure sustain various processes and have proteomic/transcriptomic/genomic patterns that would subside to developing a specific function in a specific moment of time and in a defined space. Within the complex skin structure melanocyte is one of the cell types that is involved in skin’s main functions. In the process of normal melanocyte transformation into a neoplastic cell there are several stages that are favored by a protumor inflammatory milieu. A tumorigenesis-friendly environment would increase cell’s genetic instability that will further lead to tumorigenesis and additionally to metastasis. In the environment, immune cells and immune-related molecules seminally contribute to the inflammatory landscape. Melanomagenesis is not a straight forward process. In order to take place, various factors need to collide, environmental, genetic, and immune factors must conjoint. Melanomas are heterogeneous and the transformed melanocyte has various genetic alterations, these mutations being specific to the site, to the degree of UV exposure, and/or specific for the genetic make-up of the host’s organism. This variability suggests that melanoma has more than one causal pathway. Within our paper we will snapshot the cellular identity of normal melanocyte, through benign transformed melanocyte up to a full blown tumorigenesis. Factors that are triggering these transformations(s) will be briefly highlighted.

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

“…Nevi are growth-arrested, clonal neoplasms of melanocytes, triggered by certain specific mutations in the MAPK pathway, usually BRAF V600E mutations [ 17 ]. Subsequently, the benign nevus evolves into a dysplastic nevus, which progresses through the primary tumor’s radial and vertical growth phases (RGP and VGP) and ultimately invades the dermis and regional lymph nodes, from which it metastasizes to distal sites [ 18 ]. However, current literature highlights that more than two-thirds of melanomas arise de novo in normal skin without requiring a nevus precursor [ 19 , 20 ].…”

“…Multiple environmental agents can induce inflammation; however, UV radiation remains the most prominent aggressor, resulting in significant DNA damage and reactive oxygen species (ROS) generation [ 26 ]. Inflammation has acute and chronic stages that can shift the physiological balance towards skin regeneration or tumorigenesis, depending on their intensities [ 18 , 27 ]. If the inflammation is persistent and acquires chronic attributes, it may lead to a pre-cancerous lesion in the form of a dysplastic nevus.…”

“…If detected by a fully functional immune system, this pre-cancerous lesion subsides to healing, and the melanocyte regains its physiological functions. However, if the entire process develops as a sustained chronic inflammation, it triggers a plethora of molecular and cellular networks shaping an immunosuppressive milieu that sustains skin tumorigenesis and further metastasis [ 18 , 28 ] ( Figure 1 ).…”