Bersini Simone, Moretti Matteo
Cell and Tissue Engineering Lab, IRCCS Istituto Ortopedico Galeazzi, 20161, Milan, Italy,
J Mater Sci Mater Med. 2015 May;26(5):180. doi: 10.1007/s10856-015-5520-5. Epub 2015 Apr 17.
The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases.
癌细胞从原发性肿瘤向继发性位点的转移扩散是一个复杂的多步骤过程，包括局部侵袭、血管内渗、在血流中存活以及向转移位点的血管外渗。众所周知，癌症转移遵循器官特异性途径，特定的原发性肿瘤主要向特定的一组继发性器官转移（史蒂文·佩吉特理论，1889年）。然而，毛细血管网络的循环模式和微观结构在转移扩散中也起着关键作用（詹姆斯·尤因理论，1929年）。考虑到这两个因素对于开发更复杂且生理相关性更强的体外癌症模型至关重要。本综述介绍了通过微流控方法生成微血管化系统的最新进展，并讨论了模仿特定器官功能单元病理生理学的芯片器官平台所取得的有前景的成果。生理样微血管网络和器官型微环境的结合将催生出新一代体外癌症模型，以更有效地筛选新疗法、设计个性化药物治疗方案并研究癌症转移所涉及的分子途径。
