Poon Stephanie, Ailles Laurie E
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Cancers (Basel). 2022 Feb 15;14(4):962. doi: 10.3390/cancers14040962.
The major cause of cancer-related deaths can be attributed to the metastatic spread of tumor cells-a dynamic and complex multi-step process beginning with tumor cells acquiring an invasive phenotype to allow them to travel through the blood and lymphatic vessels to ultimately seed at a secondary site. Over the years, various in vitro models have been used to characterize specific steps in the cascade to collectively begin providing a clearer picture of the puzzle of metastasis. With the discovery of the TME's supporting role in activating tumor cell invasion and metastasis, these models have evolved in parallel to accommodate features of the TME and to observe its interactions with tumor cells. In particular, CAFs that reside in reactive tumor stroma have been shown to play a substantial pro-invasive role through their matrix-modifying functions; accordingly, this warranted further investigation with the development and use of invasion assays that could include these stromal cells. This review explores the growing toolbox of assays used to study tumor cell invasion, from the simple beginnings of a tumor cell and extracellular matrix set-up to the advent of models that aim to more closely recapitulate the interplay between tumor cells, CAFs and the extracellular matrix. These models will prove to be invaluable tools to help tease out the intricacies of tumor cell invasion.
癌症相关死亡的主要原因可归因于肿瘤细胞的转移扩散——这是一个动态且复杂的多步骤过程，始于肿瘤细胞获得侵袭表型，使其能够通过血液和淋巴管移动，最终在继发部位着床。多年来，各种体外模型已被用于表征这一连串过程中的特定步骤，从而开始共同描绘出一幅更清晰的转移难题图景。随着肿瘤微环境（TME）在激活肿瘤细胞侵袭和转移中支持作用的发现，这些模型也在不断发展，以适应TME的特征并观察其与肿瘤细胞的相互作用。特别是，存在于反应性肿瘤基质中的癌症相关成纤维细胞（CAFs）已被证明通过其基质修饰功能发挥重要的促侵袭作用；因此，随着能够纳入这些基质细胞的侵袭检测方法的开发和应用，这值得进一步研究。本综述探讨了用于研究肿瘤细胞侵袭的检测方法的不断扩充的工具箱，从最初简单的肿瘤细胞与细胞外基质设置，到旨在更精确模拟肿瘤细胞、CAFs和细胞外基质之间相互作用的模型的出现。这些模型将被证明是帮助梳理肿瘤细胞侵袭复杂性的宝贵工具。
