Millet Martial, Ben Messaoud Raoua, Luthold Carole, Bordeleau Francois
CHU de Québec-Université Laval Research Center (Oncology division), Université Laval Cancer Research Center and Faculty of Medicine, Université Laval, Québec, QC G1R 3S3, Canada.
Micromachines (Basel). 2019 Jun 22;10(6):418. doi: 10.3390/mi10060418.
The tumor microenvironment (TME) is composed of dynamic and complex networks composed of matrix substrates, extracellular matrix (ECM), non-malignant cells, and tumor cells. The TME is in constant evolution during the disease progression, most notably through gradual stiffening of the stroma. Within the tumor, increased ECM stiffness drives tumor growth and metastatic events. However, classic in vitro strategies to study the TME in cancer lack the complexity to fully replicate the TME. The quest to understand how the mechanical, geometrical, and biochemical environment of cells impacts their behavior and fate has been a major force driving the recent development of new technologies in cell biology research. Despite rapid advances in this field, many challenges remain in order to bridge the gap between the classical culture dish and the biological reality of actual tissue. Microfabrication coupled with microfluidic approaches aim to engineer the actual complexity of the TME. Moreover, TME bioengineering allows artificial modulations with single or multiple cues to study different phenomena occurring in vivo. Some innovative cutting-edge tools and new microfluidic approaches could have an important impact on the fields of biology and medicine by bringing deeper understanding of the TME, cell behavior, and drug effects.
肿瘤微环境(TME)由基质底物、细胞外基质(ECM)、非恶性细胞和肿瘤细胞组成的动态复杂网络构成。在疾病进展过程中,TME处于不断演变之中,最显著的是通过基质的逐渐硬化。在肿瘤内部,ECM硬度增加会推动肿瘤生长和转移事件。然而,研究癌症中TME的经典体外策略缺乏完全复制TME的复杂性。探索细胞的机械、几何和生化环境如何影响其行为和命运,一直是推动细胞生物学研究新技术近期发展的主要动力。尽管该领域取得了快速进展,但为了弥合传统培养皿与实际组织的生物学现实之间的差距,仍存在许多挑战。微制造与微流控方法相结合旨在构建TME的实际复杂性。此外,TME生物工程允许通过单一或多种线索进行人工调节,以研究体内发生的不同现象。一些创新的前沿工具和新的微流控方法可能会对生物学和医学领域产生重要影响,通过更深入地了解TME、细胞行为和药物作用。