The role of the tumor biofilm in determining tissue tropism
The role of the tumor biofilm in determining tissue tropism
批准号:
10702590
负责人:
Kandice Tanner
金额:
$63.08万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
AdherenceAnimal ModelArchitectureBiophysical ProcessBiophysicsBlood CirculationBlood capillariesBone MarrowBrainBreast Cancer CellCancer PatientCardiovascular systemCellsChemicalsComplexCuesDistantEmbryoEnvironmentEtiologyExtravasationFishesFoundationsGeneticHomeHumanIntegrinsKnowledgeLinkMechanicsMethodsMicrobial BiofilmsModelingMusNeoplasm MetastasisOrganPatientsPatternPhasePhysiologicalRoleSignal TransductionSiteSystemTechniquesTissuesTravelZebrafishenvironmental changehuman modelin vivointravital imagingmacrophagemechanical propertiesmigrationmortalitymouse modelneoplastic celltissue mappingtissue tropismtumortumor-immune system interactions
中文摘要
细胞在循环系统中移动时会遇到无数的环境信号 系统在逮捕和进入一个遥远的器官。我们对相互作用的理解 向器官性和组织生物物理学之间的联系仍然不完整。 由于非侵入性的局限性,转移的病因学特性是困难的。 微尺度机械测绘技术和应用现有方法的能力 转移的动物模型。需要复杂的生理相关模型来重建 这些器官特异性的线索我们的大部分知识都是使用小鼠模型获得的, 解剖物理微环境在调节向器官性中的作用 技术挑战。我们还证明了斑马鱼可以作为一个可行的模型, 人肿瘤转移和人巨噬细胞迁移,因为人的转移模式 在鱼中观察到小鼠模型中的肿瘤。这一发现为 使用斑马鱼评估个体化患者免疫治疗的可能转移位点 微环境,以迅速通知患者治疗。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器官转移, 与哺乳动物系统相关的靶向。
英文摘要
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.
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海外基金