Hill David S, Robinson Neil D P, Caley Matthew P, Chen Mei, O'Toole Edel A, Armstrong Jane L, Przyborski Stefan, Lovat Penny E
Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
School of Biological and Biomedical Sciences, Durham University, Durham, United Kingdom.
Mol Cancer Ther. 2015 Nov;14(11):2665-73. doi: 10.1158/1535-7163.MCT-15-0394. Epub 2015 Sep 1.
Metastatic melanoma remains incurable, emphasizing the acute need for improved research models to investigate the underlying biologic mechanisms mediating tumor invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully humanized three-dimensional (3D) skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumor invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates that this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth-phase melanoma invasion.
转移性黑色素瘤仍然无法治愈，这凸显了迫切需要改进研究模型，以研究介导肿瘤侵袭和转移的潜在生物学机制，并开发更有效的靶向疗法来改善临床结果。现有的黑色素瘤动物模型不能准确反映人类疾病，目前包含黑色素瘤细胞的体外人皮肤等效模型也不能完全代表人类皮肤微环境。我们开发了一种强大且可重复的、完全人源化的三维（3D）皮肤等效物，它由分层的、终末分化的表皮和由成纤维细胞产生的细胞外基质组成的真皮隔室构成。纳入表皮的黑色素瘤细胞能够穿过基底膜侵入真皮，这与体内早期肿瘤侵袭情况相似。将我们新型的3D黑色素瘤皮肤等效物与原位黑色素瘤和转移性黑色素瘤进行比较表明，该模型准确地重现了疾病病理学特征，使其成为早期放射状和垂直生长期黑色素瘤侵袭的生理代表性模型。
