The role of the tumor biofilm in determining tissue tropism

细胞在被捕获并进入遥远的器官之前，在循环系统内旅行时会遇到无数的环境线索。我们对器官趋向性和组织生物物理学之间的相互作用的了解仍然不完全。此外，由于在微观尺度上的非侵入性机械标测技术的局限性以及将现有方法应用于转移的动物模型的能力，将力学特性与转移的病因联系起来是困难的。需要复杂的生理相关模型来重建这些器官特定的线索。我们的大部分知识是通过小鼠模型获得的，在这些模型中，解剖物理微环境在调节器官趋向性中的作用在技术上仍然具有挑战性。我们还证明了斑马鱼可以作为人类肿瘤转移和人巨噬细胞迁移的可行模型，因为在FISH中观察到了人类肿瘤在小鼠模型中的转移模式。这一发现为利用斑马鱼评估个性化患者免疫微环境的可能转移部位提供了基础，以迅速为患者治疗提供信息。因此，我们准备利用斑马鱼作为人类转移的模型来评估哪些物理线索可以驱动与哺乳动物系统相关的器官靶向。

Cells encounter a myriad of environmental cues as they travel within the circulation system before arrest and entry into a distant organ. Our understanding of the interplay between organotropism and tissue biophysics remains incomplete Moreover, linking mechanical properties to the etiology of metastasis are difficult due to the limitations of non-invasive techniques for mechanical mapping at the microscale and the ability to apply existing methods to animal models of metastasis. Complex physiologically relevant models are needed to recreate these organ specific cues. Much of our knowledge has been obtained using murine models where dissecting the role of the physical microenvironment in regulating organotropism remain technically challenging. We also demonstrated that zebrafish can be used as a viable model of human tumor metastasis and human macrophage migration, since patterns of metastasis of human tumors in mouse models are observed in the fish. This discovery provides the foundation for use of zebrafish to assess possible metastatic sites for individualized patient immune microenvironment to rapidly inform patient treatment. Thus, we are poised to exploit the use of zebrafish as a model of human metastasis to evaluate what physical cues may drive organ targeting relevant for mammalian systems.