Mackenzie Ian C
Department of Adult Dental Health, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XY, UK.
J Oral Pathol Med. 2004 Feb;33(2):71-8. doi: 10.1111/j.1600-0714.2004.00157.x.
Oral squamous cell carcinoma (OSCC) is associated both with the local expansion of clones of malignant cells and with their further migration to regional and distant sites. The interactions that occur between normal and malignant cells during these events are not well modelled by standard culture conditions, but organotypical cultures, in which epithelial cells are grown on a matrix containing fibroblasts, provide a suitable environment for such investigations.
Cells from five cell lines, each derived from OSCC and marked by retroviral transduction with alkaline phosphatase, were incorporated as small subpopulations (0.1-5%) in uniformly differentiating organotypical cultures constructed from normal oral mucosal cells. The patterns of growth of the malignant cells within the normal epithelium were examined for 3 weeks.
There was variation between the different cell lines in their rates and patterns of growth, but all cell lines produced clusters of malignant cells that had expanded within 3 weeks to replace the normal epithelium. The appearance and spacing of these clusters suggested that each was derived from a single progenitor cell. The number of malignant cells initially present within a given area of organotypical epithelium was much greater than the number of expanding cell clusters subsequently formed. Cluster-forming cells thus represented only a subpopulation of the tumour cells.
The organotypical model allows examination of interactions occurring between cells derived from OSCC and normal epithelia. The three-dimensional nature of organotypical cultures, together with their more normal patterns of differentiation, provides an environment that more closely mimics the in vivo environment in which tumours develop. The finding that only a subpopulation of tumour cells forms expanding tumour colonies suggests a range of growth potentials within a tumour population and may provide preliminary evidence for some form of stem and amplifying cell pattern.
口腔鳞状细胞癌（OSCC）与恶性细胞克隆的局部扩展及其向区域和远处部位的进一步迁移均有关联。在这些过程中正常细胞与恶性细胞之间发生的相互作用无法通过标准培养条件得到很好的模拟，但是器官型培养，即上皮细胞在含有成纤维细胞的基质上生长，为这类研究提供了合适的环境。
来自五个细胞系的细胞，每个细胞系均源自OSCC并通过碱性磷酸酶逆转录病毒转导进行标记，作为小亚群（0.1 - 5%）被纳入由正常口腔黏膜细胞构建的均匀分化的器官型培养物中。对正常上皮内恶性细胞的生长模式进行了3周的观察。
不同细胞系在其生长速率和模式上存在差异，但所有细胞系均产生了恶性细胞簇，这些簇在3周内扩展并取代了正常上皮。这些簇的外观和间距表明每个簇均源自单个祖细胞。在器官型上皮给定区域最初存在的恶性细胞数量远大于随后形成的扩展细胞簇的数量。因此，形成簇的细胞仅代表肿瘤细胞的一个亚群。
器官型模型允许研究源自OSCC的细胞与正常上皮之间发生的相互作用。器官型培养的三维性质及其更正常的分化模式提供了一个更紧密模拟肿瘤发生的体内环境的环境。只有肿瘤细胞的一个亚群形成扩展的肿瘤集落这一发现表明肿瘤群体内存在一系列生长潜能，并可能为某种形式的干细胞和扩增细胞模式提供初步证据。
