Department of Bioprocess Engineering, Institute for Bioprocessing and Analytical Measurement Techniques e.V. (iba), Heilbad Heiligenstadt, Germany.
Sci Rep. 2024 Aug 14;14(1):18851. doi: 10.1038/s41598-024-69261-2.
The progression of cancer cell migration, invasion and subsequent metastasis is the main cause of mortality in cancer patients. Through creating more accurate cancer models, we can achieve more precise results, which will lead to a better understanding of the invasion process. This holds promise for more effective prevention and treatment strategies. Although numerous 2D and 3D cell culture systems have been developed, they poorly reflect the in vivo situation and many questions have remained unanswered. This work describes a novel dynamic 3D cell culture system aimed at advancing our comprehension of cancer cell migration. With the newly designed cultivation chamber, 3D tumor spheroids were cultivated within a collagen I matrix in the presence of fluid flow to study the migration of cancer cells from spheroids in the matrix. Using light sheet microscopy and histology, we demonstrated that the morphology of spheroids is influenced by dynamic culture and that, in contrast to static culture, spheroids in dynamic culture are characterized by the absence of a large necrotic core. Additionally, this influence extends to an increase in the size of migration area, coupled with an increase in expression of some genes related to epithelial-mesenchymal transition (EMT). The results here highlight the importance of dynamic culture in cancer research. Although the dynamic 3D cell culture system in this study was used to investigate migration of one cell type into a matrix, it has the potential to be further developed and used for more complex models consisting of different cell types or to analyze other steps of metastasis development such as transendothelial migration or extravasation.
癌细胞的迁移、侵袭和随后的转移是癌症患者死亡的主要原因。通过创建更精确的癌症模型，我们可以获得更精确的结果，从而更好地理解侵袭过程。这为更有效的预防和治疗策略提供了希望。尽管已经开发出了许多 2D 和 3D 细胞培养系统，但它们都不能很好地反映体内情况，仍有许多问题尚未得到解答。本工作描述了一种新型的动态 3D 细胞培养系统，旨在提高我们对癌细胞迁移的理解。使用新设计的培养室，在存在流体流动的情况下，将 3D 肿瘤球体在胶原 I 基质中培养，以研究癌细胞从基质中的球体迁移。通过使用光片显微镜和组织学，我们证明了动态培养会影响球体的形态，与静态培养相比，动态培养的球体的特征是没有大的坏死核心。此外，这种影响还扩展到迁移区域的增大，伴随着与上皮-间充质转化（EMT）相关的一些基因表达的增加。本研究结果强调了动态培养在癌症研究中的重要性。尽管本研究中的动态 3D 细胞培养系统用于研究一种细胞类型向基质中的迁移，但它具有进一步发展和用于更复杂模型（包括不同细胞类型）的潜力，或者用于分析转移发展的其他步骤，如跨内皮迁移或外渗。
