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.

在逮捕和进入遥远的器官之前，细胞在循环系统中传播时会遇到无数的环境提示。我们对有机体和组织生物物理学之间的相互作用的理解仍然不完整，由于无侵入性技术在显微镜上的机械映射的局限性以及将现有方法应用于转移模型的能力，因此很难将机械性能与转移的病因联系起来。需要复杂的生理相关模型来重新创建这些器官特定的线索。我们的大部分知识是使用鼠模型获得的，在这种模型中，剖析物理微环境在调节器官质主义中的作用仍然具有挑战性。我们还证明，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了小鼠模型中人类肿瘤转移的模式。这一发现为使用斑马鱼评估个性化患者免疫微环境的转移部位提供了基础，以迅速为患者治疗提供信息。因此，我们有望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会驱动与哺乳动物系统相关的器官靶向。