Leggett Susan E, Khoo Amanda S, Wong Ian Y
School of Engineering, Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA.
Biomater Sci. 2017 Jul 25;5(8):1460-1479. doi: 10.1039/c7bm00272f.
Cancer cell invasion through the extracellular matrix is associated with metastatic spread and therapeutic resistance. In carcinomas, the detachment and dissemination of individual cells has been associated with an epithelial-mesenchymal transition, but tumors can also invade using collective, multicellular phenotypes. This malignant tumor progression is also associated with alignment and stiffening of the surrounding extracellular matrix. Historically, tumor invasion has been investigated using 2D monolayer culture, small animal models or patient histology. These assays have been complemented by the use of natural biomaterials such as reconstituted basement membrane and collagen I. More recently, engineered materials with well-defined physical, chemical and biomolecular properties have enabled more controlled microenvironments. In this review, we highlight recent developments in multicellular tumor invasion based on microfabricated structures or hydrogels. We emphasize the role of interfacial geometries, biomaterial stiffness, matrix remodeling, and co-culture models. Finally, we discuss future directions for the field, particularly integration with precision measurements of biomaterial properties and single cell heterogeneity, standardization and scale-up of these platforms, as well as integration with patient-derived samples.
癌细胞通过细胞外基质的侵袭与转移扩散和治疗抗性相关。在癌中，单个细胞的脱离和播散与上皮-间质转化有关，但肿瘤也可利用集体性的多细胞表型进行侵袭。这种恶性肿瘤进展还与周围细胞外基质的排列和硬化有关。历史上，肿瘤侵袭一直通过二维单层培养、小动物模型或患者组织学进行研究。这些检测方法通过使用天然生物材料如重组基底膜和I型胶原得到了补充。最近，具有明确物理、化学和生物分子特性的工程材料能够实现更可控的微环境。在本综述中，我们重点介绍基于微纳加工结构或水凝胶的多细胞肿瘤侵袭的最新进展。我们强调界面几何形状、生物材料硬度、基质重塑和共培养模型的作用。最后，我们讨论该领域的未来方向，特别是与生物材料特性和单细胞异质性的精确测量相结合、这些平台的标准化和扩大规模，以及与患者来源样本的整合。
