Development and characterization of a three-dimensional co-culture model of tumor T cell infiltration
Development and characterization of a three-dimensional co-culture model of tumor T cell infiltration
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DOI：
10.1088/1758-5090/8/2/025002
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发表时间：
2016-06-01
期刊：
影响因子：
9
通讯作者：
de la Fuente, M.
中科院分区：
文献类型：
--
作者：
Alonso-Nocelo, M.;Abuin, C.;de la Fuente, M.
肿瘤生长和转移涉及非恶性细胞的改变和向原发性肿瘤的募集，其中免疫细胞构成肿瘤微环境（TME）。肿瘤细胞与其间质之间的通讯已被证明是肿瘤过程的基本驱动力。大量的努力集中在描绘他们的具体互动和串扰。然而，大多数研究都是在改变细胞形态和细胞内信号传导过程的2D传统培养中进行的。考虑到这些前提，我们开发了一个3D细胞共培养模型来模拟T细胞浸润到肿瘤块中，并探索TME中肿瘤-免疫细胞的相互作用。进行特异性细胞标志物的表达和细胞增殖的评估以表征所提出的3D共培养模型。此外，对分泌组的研究和分析揭示了在淋巴细胞存在下肿瘤细胞的3D培养后提示的特定癌症相关炎症蛋白的子集，指出了细胞间的通信。总而言之，这些结果表明，我们的3D细胞共培养模型可以成为识别和研究介导TME中肿瘤和免疫细胞之间串扰的关键因素的有用工具。最后，使用多西他赛作为模型抗肿瘤化合物，探索了该模型作为药物筛选平台的潜力。
Tumor growth and metastasis entangle the alteration and recruitment of non-malignant cells to the primary tumor, among them immune cells, constituting the tumor microenvironment (TME). Communication between tumor cells and their stroma has been shown as a fundamental driving force of the tumoral process. A great deal of effort has been focused on depicting their specific interactions and crosstalk. However, most research has been carried out in 2D conventional cultures that alter cell morphology and intracellular signaling processes. Considering these premises, we have developed a 3D cell co-culture model to mimic T cell infiltration into the tumor mass and explore tumor-immune cells interactions in the TME. Expression of specific cell markers and assessment of cell proliferation were carried out to characterize the proposed 3D co-culture model. Additionally, the study and profiling of the secretome revealed a subset of particular cancer-related inflammation proteins prompted upon 3D cultivation of tumor cells in presence of lymphocytes, pointing out an intercellular communication. Altogether, these results suggest that our 3D cell co-culture model can be a useful tool to identify and study critical factors mediating the crosstalk between tumor and immune cells in the TME. Finally, the potential of this model as a drug-screening platform has been explored using docetaxel as a model antitumoral compound.