Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Zurich, Switzerland.
J Invest Dermatol. 2012 Jan;132(1):144-53. doi: 10.1038/jid.2011.275. Epub 2011 Sep 1.
To overcome the lack of effective therapeutics for aggressive melanoma, new research models closely resembling the human disease are required. Here we report the development of a fully orthotopic, humanized in vivo model for melanoma, faithfully recapitulating human disease initiation and progression. To this end, human melanoma cells were seeded into engineered human dermo-epidermal skin substitutes. Transplantation onto the back of immunocompromised rats consistently resulted in the development of melanoma, displaying the hallmarks of their parental tumors. Importantly, all initial steps of disease progression were recapitulated, including the incorporation of the tumor cells into their physiological microenvironment, transition of radial to vertical growth, and establishment of highly vascularized, aggressive tumors with dermal involvement. Because all cellular components can be individually accessed using this approach, it allows manipulation of the tumor cells, as well as of the keratinocyte and stromal cell populations. Therefore, in one defined model system, tumor cell-autonomous and non-autonomous pathways regulating human disease progression can be investigated in a humanized, clinically relevant context.
为了克服侵袭性黑色素瘤缺乏有效治疗方法的问题，需要开发更接近人类疾病的新型研究模型。在这里，我们报告了一种完全原位、人源化的黑色素瘤体内模型的开发，该模型忠实地再现了人类疾病的起始和进展。为此，我们将人黑色素瘤细胞接种到工程化的人真皮表皮皮肤替代物中。将其移植到免疫缺陷大鼠的背部，会持续产生黑色素瘤，并显示出其亲本肿瘤的特征。重要的是，疾病进展的所有初始步骤都得到了再现，包括肿瘤细胞融入其生理微环境、从横向生长到垂直生长的转变，以及建立具有真皮浸润的高度血管化、侵袭性肿瘤。由于可以使用这种方法单独访问所有细胞成分，因此它可以对肿瘤细胞以及角质形成细胞和基质细胞群进行操作。因此，在一个明确的模型系统中，可以在人源化的、临床相关的背景下研究调节人类疾病进展的肿瘤细胞自主和非自主途径。
