The role of the tumor biofilm in determining tissue tropism

细胞在进入远端器官之前，在循环系统中行进时会遇到无数的环境信号。我们对器官亲和性和组织生物物理学之间的相互作用的理解仍然不完整。此外，由于在微观尺度上进行机械制图的非侵入性技术的限制以及将现有方法应用于转移动物模型的能力，将机械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异性线索。我们的大部分知识都是通过小鼠模型获得的，在小鼠模型中，解剖物理微环境在调节器官亲和性中的作用在技术上仍然具有挑战性。我们还证明斑马鱼可以作为人类肿瘤转移和人类巨噬细胞迁移的可行模型，因为在小鼠模型中可以观察到人类肿瘤的转移模式。这一发现为利用斑马鱼评估可能的转移部位、个性化患者免疫微环境以快速告知患者治疗提供了基础。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能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.