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

• Published in: Scientific reports Vol. 8; no. 1; pp. 13191 - 13
• Main Authors: Bourland, Jennifer, Fradette, Julie, Auger, François A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.09.2018; Nature Publishing Group
• Subjects: 13/106; 13/107; 14/1; 14/19; 14/34; 631/67; 631/80; 82; 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-31502-6

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.