The role of the tumor biofilm in determining tissue tropism

肿瘤生物膜在确定组织向性中的作用

• 批准号: 10486886
• 负责人: Kandice Tanner
• 金额: $ 59.3万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10486886
• 关键词: Adherence; Animal Model; Architecture; Biophysical Process; Biophysics; Blood Circulation; Blood capillaries; Bone Marrow; Brain; Breast Cancer Cell; Cancer Patient; Cardiovascular system; Cells; Chemicals; Complex; Cues; Distant; Embryo; Environment; Etiology; Extravasation; Fishes; Foundations; Genetic; Home; Human; Integrins; Knowledge; Link; Mechanics; Methods; Microbial Biofilms; Modeling; Mus; Neoplasm Metastasis; Organ; Patients; Pattern; Phase; Physiological; Role; Signal Transduction; Site; System; Techniques; Tissues; Travel; Zebrafish; environmental change; human model; in vivo; intravital imaging; macrophage; mechanical properties; migration; mortality; mouse model; neoplastic cell; tissue tropism; tumor; tumor-immune system interactions

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.

当细胞在循环系统中移动时，它们会遇到无数的环境线索，然后被逮捕并进入远处的器官。我们对向器官性和组织生物物理学之间的相互作用的理解仍然是不完整的。此外，由于在微观尺度上进行机械映射的非侵入性技术的局限性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使用小鼠模型获得的，其中解剖物理微环境在调节向器官性中的作用仍然具有技术挑战性。我们还证明了斑马鱼可以用作人类肿瘤转移和人类巨噬细胞迁移的可行模型，因为在鱼类中观察到小鼠模型中人类肿瘤的转移模式。这一发现为使用斑马鱼评估可能的转移位点提供了基础，以获得个性化的患者免疫微环境，从而快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，以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。