Commandeur Suzan, de Gruijl Frank R, Willemze Rein, Tensen Cornelis P, El Ghalbzouri Abdoelwaheb
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Exp Dermatol. 2009 Oct;18(10):849-56. doi: 10.1111/j.1600-0625.2009.00856.x. Epub 2009 Mar 12.
Squamous cell carcinomas (SCC) represent a substantial clinical problem because of increases, frequent recurrences and successive de novo tumors, especially in organ transplant recipients. To improve upon the current surgical and other non-selective therapies, a validated organotypic in vitro model of primary human SCC needs to be developed. Such a model will have obvious advantages over current cell line and animal based approaches, and may render the latter partly obsolete. In a first approach, an explant technique of primary SCC biopsies onto dermal constructs was used to emulate tumor expansion in an in vitro model. Histological analysis revealed the formation of nests of squamous cells, mimicking an invasive morphological feature of primary SCC. Immunohistochemical analysis comprised an array of markers characteristic of keratinocyte (hyper) proliferation (K6, K16, K17 and Ki67), differentiation (K1, K10 and involucrin), basement membrane (collagen types IV and VII, integrins alpha(6) and beta(4) and laminin 332) and SCC (K4, K13 and Axl). The generated human SCC models displayed disturbed differentiation and keratins associated with hyperproliferation, but a low frequency of Ki67 positive cells. Basement membrane composition of the in vitro SCC model resembled that of normal skin. These results show for the first time that in vitro modelling of three-dimensional growth of primary cutaneous human SCC is feasible. This model may provide a platform to develop refined preventive and curative treatments and thereby gain understanding of SCC pathogenesis.
鳞状细胞癌（SCC）是一个严重的临床问题，因为其发病率上升、频繁复发以及相继出现新发肿瘤，尤其是在器官移植受者中。为了改进当前的手术及其他非选择性治疗方法，需要开发一种经过验证的原发性人类SCC的体外器官型模型。这样的模型将比当前基于细胞系和动物的方法具有明显优势，并且可能会使后者部分过时。在第一种方法中，采用将原发性SCC活检组织植入真皮构建体的外植体技术，以在体外模型中模拟肿瘤扩展。组织学分析显示形成了鳞状细胞巢，模拟了原发性SCC的侵袭性形态特征。免疫组织化学分析包括一系列角质形成细胞（过度）增殖（K6、K16、K17和Ki67）、分化（K1、K10和内披蛋白）、基底膜（IV型和VII型胶原蛋白、整合素α(6)和β(4)以及层粘连蛋白332）和SCC（K4、K13和Axl）的特征性标志物。所生成的人类SCC模型显示出分化紊乱以及与过度增殖相关的角蛋白，但Ki67阳性细胞的频率较低。体外SCC模型的基底膜组成类似于正常皮肤。这些结果首次表明，原发性皮肤人类SCC三维生长的体外建模是可行的。该模型可能提供一个平台，以开发精细的预防和治疗方法，从而深入了解SCC的发病机制。
