Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development

While being the rarest skin cancer, melanoma is also the deadliest. To further drug discovery and improve clinical translation, new human cell-based in vitro models are needed. Our work strives to mimic the melanoma microenvironment in vitro as an alternative to animal testing. We used the self-asse...

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Bibliographic Details
Published in:Scientific reports 2018-09, Vol.8 (1), p.13191-13, Article 13191
Main Authors: Bourland, Jennifer, Fradette, Julie, Auger, François A.
Format: Article
Language:English
Subjects:
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Animal research
Antineoplastic Agents - pharmacology
Apoptosis
Biomaterials
Blood
Capillaries
Cell culture
Cell Line
Cell Line, Tumor
Cell Proliferation - drug effects
Drug development
Drug Development - methods
Drug Screening Assays, Antitumor - methods
Epidermis
Extracellular matrix
Filaggrin
Filaggrin Proteins
Humanities and Social Sciences
Humans
Laminin
Lymphatic Vessels - drug effects
Lymphatic Vessels - pathology
Melanoma
Melanoma - blood supply
Melanoma - drug therapy
Melanoma - pathology
multidisciplinary
Science
Science (multidisciplinary)
Self-assembly
Skin cancer
Skin Neoplasms - blood supply
Skin Neoplasms - drug therapy
Skin Neoplasms - pathology
Tissue engineering
Tissue Engineering - methods
Tumor Microenvironment - drug effects
Vemurafenib - pharmacology
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Description
Summary:While being the rarest skin cancer, melanoma is also the deadliest. To further drug discovery and improve clinical translation, new human cell-based in vitro models are needed. Our work strives to mimic the melanoma microenvironment in vitro as an alternative to animal testing. We used the self-assembly method to produce a 3D human melanoma model exempt of exogenous biomaterial. This model is based on primary human skin cells and melanoma cell lines while including a key feature for tumor progression: blood and lymphatic capillaries. Major components of the tumor microenvironment such as capillaries, human extracellular matrix, a stratified epidermis (involucrin, filaggrin) and basement membrane (laminin 332) are recapitulated in vitro . We demonstrate the persistence of CD31 + blood and podoplanin + /LYVE-1 + lymphatic capillaries in the engineered tissue. Chronic treatment with vemurafenib was applied to the model and elicited a dose-dependent response on proliferation and apoptosis, making it a promising tool to test new compounds in a human-like environment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-31502-6