Abstract：
In cancer metastasis, where mortality rates remain high despite advancements in medical treatments, understanding the molecular pathways and cellular dynamics underlying tumor spread is critical for devising more effective therapeutic strategies. Here, a folding paper system was proposed and developed to mimic native tumor microenvironment. This system, composed of 7 stacked layers of paper enclosed in a holder, allows for the culture of cancer cells under conditions mimicking those found in solid tumors, including limited oxygen and nutrients. Because of the migratory capabilities of cancer cells, the cells in the center layer could migrated to outer layers of the paper stack, enabling the differentiation of cells based on their migratory potential. Subsequent gene expression analysis, conducted through RT-PCR and RNA sequencing, revealed significant correlations between cancer cell migration distance and the expression of genes associated with hypoxia, metabolism, ATP production, and cellular process. Moreover, our study identified cells with aggressive phenotypic traits from the outer layers of the paper stack, highlighting the potential of this system for enabling the study of aggressive cancer cell characteristics. Validation of the folding paper system against clinical carcinoma tissue demonstrated its ability to faithfully mimic the native tumor microenvironment. Overall, our findings underscore the utility of the folding paper system as a valuable tool for investigating and identifying critical molecular pathways involved in cancer metastasis.
摘要：
在癌症转移中，尽管医学治疗取得了进步，但死亡率仍然很高，了解肿瘤扩散的分子途径和细胞动力学对于设计更有效的治疗策略至关重要.这里,提出并开发了一种折叠纸系统来模拟天然肿瘤微环境。这个系统,由封装在支架中的7层堆叠的纸张组成，允许在模拟实体瘤中发现的条件下培养癌细胞，包括有限的氧气和营养。由于癌细胞的迁移能力，中心层的细胞可以迁移到纸堆的外层，使细胞能够根据其迁移潜力进行分化。随后的基因表达分析，通过RT-PCR和RNA测序，揭示了癌细胞迁移距离与缺氧相关基因表达之间的显著相关性，新陈代谢，ATP生产，细胞过程。此外，我们的研究从纸堆的外层确定了具有侵袭性表型特征的细胞，强调了该系统在研究侵袭性癌细胞特征方面的潜力。针对临床癌组织的折叠纸系统的验证证明了其忠实地模拟天然肿瘤微环境的能力。总的来说,我们的研究结果强调了折叠纸系统作为研究和识别与癌症转移有关的关键分子通路的有价值工具的实用性.
