Progress in melanoma modelling in vitro

Abstract

Melanoma is one of the most studied neoplasia, although laboratory techniques used for investigating this tumor are not fully reliable. Animal models may not predict the human response due to differences in skin physiology and immunity. In addition, international guidelines recommend to develop processes that contribute to the reduction, refinement and replacement of animals for experiments (3Rs). Adherent cell culture has been widely used for the study of melanoma to obtain important information regarding melanoma biology. Nonetheless, these cells grow in adhesion on the culture substrate which differs considerably from the situation in vivo. Melanoma grows in a 3D spatial conformation where cells are subjected to a heterogeneous exposure to oxygen and nutrient. In addition, cell-cell and cell-matrix interaction play a crucial role in the pathobiology of the tumor as well as in the response to therapeutic agents. To better study, melanoma new techniques, including spherical models, tumorospheres and melanoma skin equivalents, have been developed. These 3D models allow to study tumors in a microenvironment that is more close to the in vivo situation and are less expensive and time-consuming than animal studies. This review will also describe the new technologies applied to skin reconstructs such as organ-on-a-chip that allows skin perfusion through microfluidic platforms. 3D in vitro models, based on the new technologies, are becoming more sophisticated, representing at a great extent the in vivo situation, the "perfect" model that will allow less involvement of animals up to their complete replacement, is still far from being achieved.

Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

“…Employment of other cell types can further increase the complexity of the acquired model. These heterogeneous spheroids are an intermediate stage between non-complex 2D cultures and in vivo animal models [28][29][30]. The addition of dermal fibroblasts achieves the goal of making in vitro melanoma heterogeneous spheroids better resemble the melanoma tumour.…”

Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

“…BioMed Research International have been several attempts to include specific components of the melanoma TME to better study its pathophysiology [183,187]. Indeed, such models can help elucidate invasive mechanisms of this cancer through its interaction with fibroblasts and keratinocytes [184,185].…”

“…To summarize, 3D skin models of melanoma have the potential to provide relevant information on melanoma progression, invasion, and response to therapeutics. These models may constitute interesting alternatives to animal studies by allowing them to investigate specific questions [183,187]. Hence, it is reasonable to envision that 3D skin models will be increasingly used as research tools to decipher specific mechanisms related to metastatic progression and the development of therapeutics in melanoma.…”

Advances in the Biofabrication of 3D Skin in vitro: Healthy and Pathological Models

“…Hill et al recapitulated an invasive melanoma using rat melanoma cells in a 3D skin equivalent, thus demonstrating the current feasibility of introducing primary cells into a 3D skin model in vitro (Hill et al, 2015 ). Marconi et al have demonstrated the importance of cell-cell and cell-ECM interactions in a 3D skin model of melanoma (Marconi et al, 2018 ). Moreover, modeling these cancers in reproducible and physiological 3D skin constructs would improve personalized drug screening.…”