State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China.
Biofabrication. 2018 Oct 30;11(1):015004. doi: 10.1088/1758-5090/aae270.
Cancer biology and drug discovery are heavily dependent on conventional 2D cell culture systems. However, a 2D culture is significantly limited by its ability to reflect 'true biology' of tumor in vivo. Three-dimensional (3D) in vitro cell culture models have been introduced to aid cancer drug discovery by better modeling the tumor microenvironment. Here, decellularized lung scaffolds cultured with MCF-7 cancer cells were bioengineered as a platform to study tumor development and anti-cancer drug evaluation. Excellent cell compatibility of decellularized lung scaffolds promoted cell growth and proliferation. Multicellular tumor cell spheroids (tumoriods) were formed and enlarged exclusively in decellularized lung scaffolds over time. The expression of breast cancer biomarkers (BRCA1 and HER2) in MCF-7 cells significantly increased in the lung matrix compared to those cultured in 2D systems. Insufficient oxygen and nutrient diffusion into the internal surface of lung scaffolds resulted in intracellular hypoxia, quantified by a significant upregulation of HIF-1α protein expression compared to that of cell monolayers. Higher survival rates after exposure to 5-FU were observed in lung scaffolds (52.04%) compared to that in 2D systems (18.39%) on day 3 of culture. Overall, this new breast tumor system provides a promising platform to study breast cancer progression and develop new targeted therapeutic strategies.
癌症生物学和药物发现严重依赖于传统的 2D 细胞培养系统。然而，2D 培养在反映体内肿瘤“真实生物学”方面的能力受到显著限制。三维（3D）体外细胞培养模型已被引入，以通过更好地模拟肿瘤微环境来辅助癌症药物发现。在这里，用 MCF-7 癌细胞培养的去细胞化肺支架被生物工程化为一个研究肿瘤发展和抗癌药物评价的平台。去细胞化肺支架具有出色的细胞相容性，可促进细胞生长和增殖。随着时间的推移，多细胞肿瘤细胞球（肿瘤球）仅在去细胞化肺支架中形成并增大。与在 2D 系统中培养相比，MCF-7 细胞中乳腺癌生物标志物（BRCA1 和 HER2）的表达在肺基质中显著增加。由于氧气和营养物质向肺支架内部表面的扩散不足，导致细胞内缺氧，通过与细胞单层相比，HIF-1α 蛋白表达的显著上调来定量。在培养的第 3 天，暴露于 5-FU 后在肺支架（52.04%）中的存活率高于在 2D 系统（18.39%）中的存活率。总体而言，这种新的乳腺癌肿瘤系统为研究乳腺癌进展和开发新的靶向治疗策略提供了一个有前途的平台。
