A Novel Organotypic Model Mimics the Tumor Microenvironment
A Novel Organotypic Model Mimics the Tumor Microenvironment
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DOI：
10.2353/ajpath.2009.081110
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发表时间：
2009-09-01
影响因子：
6
通讯作者：
Salo, Tuula
中科院分区：
文献类型：
--
作者：
Nurmenniemi, Sini;Sinikumpu, Teemu;Salo, Tuula
癌细胞的侵袭传统上是在由I型胶原和成纤维细胞组成的三维器官型模型中研究的。然而，癌细胞的行为受到肿瘤微环境中各种细胞类型和细胞外基质（ECM）的影响。本研究建立了一种基于人子宫平滑肌瘤组织的新型器官型模型，并对其进行了表征，为癌细胞创造了更真实的生长环境。将人舌鳞癌细胞（HSC-3）分别培养在胶原蛋白和肌瘤上。通过免疫组织化学和原位杂交检查器官型切片。与胶原相比，肌瘤中HSC-3细胞的最大浸润深度明显增加。在肌瘤中，存在多种细胞类型和ECM成分，在肌瘤模型中HSC-3细胞仅表达ECM分子。用放射免疫法、酶谱法或Western blotting分析器官型培养基。在癌细胞侵袭过程中，基质金属蛋白酶-9的产生和胶原蛋白的降解增强，尤其是在肌瘤模型中。为了评估肌瘤模型的普遍适用性，我们在肌瘤上培养了几种口腔癌、乳腺癌和黑色素瘤细胞系，发现它们以高度不同的模式侵袭。我们得出结论，肌瘤组织比以前的器官型模型更能模拟天然肿瘤微环境，并可能促进上皮细胞向间质细胞的转化。因此，肌瘤模型为分析癌细胞的行为提供了一个很有前途的工具。（美国病理学杂志，2009,175:1281-1291;DOI: 10.2353/ajpath.2009.081110）
Carcinoma cell invasion is traditionally studied in three-dimensional organotypic models composed of type I collagen and fibroblasts. However, carcinoma cell behavior is affected by the various cell types and the extracellular matrix (ECM) in the tumor microenvironment. in this study, a novel organotypic model based on human uterine leiomyoma tissue was established and characterized to create a more authentic environment for carcinoma cells. Human tongue squamous cell carcinoma cells (HSC-3) were cultured on top of either collagen or myoma. Organotypic sections were examined by immunohistochemistry and in situ hybridization. The maximal invasion depth of HSC-3 cells was markedly increased in myomas compared with collagen. in myomas, various cell types and ECM components were present, and the HSC-3 cells only expressed ECM molecules in the myoma model. Organotypic media were analyzed by radioimmunoassay, zymography, or Western blotting. During carcinoma cell invasion, matrix metalloprotease-9 production and collagen degradation were enhanced particularly in the myoma model. To evaluate the general applicability of the myoma model, several oral carcinoma, breast carcinoma, and melanoma cell lines were cultured on myomas and found to invade in highly distinct patterns. We conclude that myoma tissue mimics the native tumor microenvironment better than previous organotypic models and possibly enhances epithelial-to-mesenchymal transition. Thus, the myoma model provides a promising tool for analyzing the behavior of carcinoma cells. (Am J Pathol 2009, 175:1281-1291; DOI: 10.2353/ajpath.2009.081110)