Stem Cell-Derived Models of Neural Crest Are Essential to Understand Melanoma Progression and Therapy Resistance

Abstract

During development, neural crest (NC) cells are early precursors of several lineages including melanocytes. Along their differentiation from multipotent cells to mature melanocytes, NC cells will go through successive steps which require either proliferative or motile capacities. For example, they will undergo Epithelial to Mesenchymal Transition (EMT) in order the separate from the neural tube and migrate to their final location in the epidermis ( Larribere and Utikal, 2013 ; Skrypek et al., 2017 ). The differentiated melanocytes are the cells of origin of melanoma tumors which progress through several stages such as radial growth phase, vertical growth phase, metastasis formation, and often resistance to current therapies. Interestingly, depending on the stage of the disease, melanoma tumor cells share phenotypes with NC cells (proliferative, motile, EMT). These phenotypes are tightly controlled by specific signaling pathways and transcription factors (TFs) which tend to be reactivated during the onset of melanoma. In this review, we summarize first the main TFs which control these common phenotypes. Then, we focus on the existing strategies used to generate human NCs. Finally we discuss how identification and regulation of NC-associated genes provide an additional approach to improving current melanoma targeted therapies.

Decoding the Role of CD271 in Melanoma

“…Brain metastases (BM) are most challenging [ 55 ] and develop in 20–40% of melanoma cases during the course of disease, with unclear subtype specificity, as reviewed by Redmer [ 56 ]. The efficient systemic dissemination of melanoma cells relies on the maintenance of a migratory phenotype, which is likely inherited from NC cells [ 57 , 58 ]. Likely, the metastatic niche plays an important role for the maintenance of the migratory phenotype.…”

The role of teratogens in neural crest development

“…NC biology has made great advances during the last 20 years, with findings that highlight the role of this cell population in vertebrate development. Moreover, due to its stem cell and migratory nature, NCCs have become a model for cancer therapy and stem cell research, with a strong focus on regenerative medicine (Larribere & Utikal, ; Liu & Cheung, ). In addition, a new classification for NCPs has been proposed that takes into account recent knowledge, new inclusion criteria and causal mechanisms of NCPs, and a detailed contribution of each NCCs population to the final outcome of the pathology has been examined (Vega‐Lopez et al, ).…”

Cutaneous melanoma dissemination is dependent on the malignant cell properties and factors of intercellular crosstalk in the cancer microenvironment (Review)

“…Every individual signalling molecule has either individual or combinatorial roles in transcriptional regulation ( 25 ). The precise understanding of this mechanism seems to be critically important because similar pathways are activated in malignancy, and they could control the biological properties of malignant CMM cells ( 26 ). The signalling pathways regulating epithelial to mesenchymal transition (EMT) can be triggered by transcription factors that are active in both NC development and cancer progression ( 27 ).…”