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.
Highlights
Malignant melanoma (MM) is a highly aggressive cancer of the skin originating from melanocytes
The latest estimate of mutation burdens is of ∼17 mutations per Mb calculated by ev TCGA from whole-exome sequencing (WES) of 318 primary and metastatic melanomas originating from non-glabrous skin
We previously demonstrated that in melanoma multicellular tumor spheroid (MCTS) the expression level of several melanoma markers (CD271, HIF-1α, ABCB5 and Oct4) observed in skin lesion and freshly isolated cells are maintained in spheroids derived from the same patients up to 168h
Summary
Malignant melanoma (MM) is a highly aggressive cancer of the skin originating from melanocytes. Zebrafish model iew represents an alternative xenotransplant model in vivo that offers a rapid, efficient approach for assessing drug effects on human cancer cells at various stages of tumorigenesis [1318]. . Many industries highlight the 3Rs as part of their corporate social responsibility, while the academic science base new exciting technologies, including stem cell, 3-dimensional (3D) tissue constructs, bioprinting and organ-on-chips are being developed. The availability of such systems and the easy access to melanoma cells have leaded to the development of various 2D and 3D melanoma models in vitro, whereby many questions will likely be addressed, without the use of animals
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