Project 3: Physical and Metabolic Constraints of Cancer Cell Invasion
项目3:癌细胞侵袭的物理和代谢限制
基本信息
- 批准号:9187703
- 负责人:
- 金额:$ 38.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AddressAdhesionsAdoptedAffectAnabolismArchitectureBiologicalBiomechanicsBiophysical ProcessBiophysicsBiosensorBlocking AntibodiesBreast Cancer CellCell AdhesionCell LineCell surfaceCellsCellular Metabolic ProcessCellular StructuresCessation of lifeClinicalCollaborationsCombined Modality TherapyComplementComputer SimulationConsumptionDataDecision MakingDevelopmentEnvironmentEvaluationFaceFrictionGlycocalyxGoalsImageImmigrationIn VitroIndividualIntegrinsInterventionIntrinsic factorInvadedLabelLamin Type ALinkMalignant NeoplasmsMechanicsMesenchymalMetabolicMetabolic PathwayMetabolic stressMetabolismMicrofabricationMigration AssayModelingModusMonitorNeoplasm MetastasisNuclearOutcomePathway interactionsPatientsPhysical environmentPhysicsPolysaccharidesPrimary NeoplasmProcessPropertyReportingResearchSamplingSignal TransductionTherapeuticTissuesWorkcancer cellcell motilitycomputer frameworkcostdeprivationextracellularhypoxia inducible factor 1imaging platformimprovedin vitro Assayin vivoinsightinterstitialintravital imagingintravital microscopymicrovesiclesmigrationphysical processphysical propertypreventprogramsresearch studyresponsesuccesstherapy outcometumortumor metabolism
项目摘要
Project Summary – Project 3
Project 3 will investigate the physical and metabolic constraints of cancer cell invasion. Cancer cell invasion
from the primary tumor into surrounding tissues is a crucial step of the metastatic cascade, which is
responsible for the vast majority of all cancer deaths. Invading cancer cells can use a number of different
`migration modes' for this process. As cells can dynamically switch between these modes, therapeutic attempts
to target specific migration mechanisms have had limited clinical success. Gaining an improved understanding
of the physical and biological mechanisms that govern the toggling between different migration modes could
provide new clues for more robust therapeutic interference to reduce or eliminate metastasis. One important
factor that has not been examined previously is how the metabolic status of individual cells can determine their
migration mode and metastatic spreading. As cancer cells pass through tight interstitial spaces and metabolite-
poor regions in vivo, they face substantial physical and metabolic challenges. We propose that invading cancer
cells must expend significant energy to penetrate such environments and adopt migration modes that minimize
metabolic cost. Cancer cell metabolism can also impact cellular structure and composition by fueling
biosynthetic pathways, which could alter cell surface architecture and nuclear deformability, and thereby
promote migration through tight spaces. The proposed research will utilize the project team's complementary
expertise in cell migration, subcellular biomechanics, intravital microscopy, and metabolic pathways and
interference. Aim 1 addresses how the physical microenvironment and adhesion/friction between the cell and
the extracellular environment determine energy consumption during different types of cell migration. Aim 2 will
investigate how physical factors intrinsic to the cell, particularly nuclear deformability and the physical
properties of the cell surface, modulate metabolic cost and migration efficiency in physiologically relevant
environments. It will further determine how metabolic reprogramming in cancer cells affects these cellular
mechanical properties and thereby modulates migration efficiency. Aim 3 will investigate the plasticity of
cancer cell migration, both in response to varying physical and metabolic challenges and to pharmacological
interference. The experimental work in each aim will be complemented by modeling of cancer cell metabolism
and physical interaction with the microenvironment, with the objective to predict outcomes of therapeutic
metabolic interventions and to identify strategies to counter adaptive responses. Project 3 will interact with both
Cores. The Tissue Microfabrication Core will provide biological samples and platforms for migration assays;
the Biophysics & Metabolic Imaging Core assists with metabolic analysis and imaging platforms. Projects 1
and 2 will contribute data and insights for a comprehensive computational modeling framework of cell
metabolism in migration; Project 2 will additionally provide tumor microvesicles for functional evaluation.
项目概要-项目3
项目3将研究癌细胞侵袭的物理和代谢限制。癌细胞侵袭
从原发肿瘤转移到周围组织是转移级联的关键步骤,
导致了绝大多数癌症死亡。入侵的癌细胞可以使用许多不同的
这一过程的“迁移模式”。由于细胞可以在这些模式之间动态切换,
靶向特定迁移机制的方法临床成功有限。获得更好的理解
控制不同迁移模式之间切换的物理和生物机制可以
为更强有力的治疗干预提供了新的线索,以减少或消除转移。一个重要
一个以前没有研究过的因素是单个细胞的代谢状态如何决定它们的代谢状态。
迁移方式和转移扩散。当癌细胞通过紧密的间隙和代谢物-
在体内的贫困地区,他们面临着巨大的物理和代谢挑战。我们认为入侵的癌症
细胞必须消耗大量的能量来穿透这样的环境,并采用最小化
代谢成本癌细胞代谢也可以影响细胞结构和组成,
生物合成途径,可以改变细胞表面结构和核变形能力,从而
通过狭小的空间促进移徙。拟议的研究将利用项目小组的补充
在细胞迁移,亚细胞生物力学,活体显微镜,代谢途径和
干扰目的1说明了物理微环境和细胞与细胞之间的粘附/摩擦如何影响细胞的生长。
细胞外环境决定了不同类型细胞迁移期间的能量消耗。目标2将
研究细胞内在的物理因素,特别是核变形能力和物理因素,
细胞表面的性质,调节生理相关的代谢成本和迁移效率,
环境.它将进一步确定癌细胞中的代谢重编程如何影响这些细胞,
机械性能,从而调节迁移效率。目标3将研究的可塑性
癌细胞迁移,无论是在响应不同的物理和代谢的挑战和药理学
干扰每个目标的实验工作将通过建立癌细胞代谢模型来补充
以及与微环境的物理相互作用,目的是预测治疗的结果。
代谢干预,并确定应对适应性反应的策略。项目3将与两者互动
丹组织微加工核心将提供生物样本和迁移分析平台;
生物物理学和代谢成像核心协助代谢分析和成像平台。项目1
和2将为细胞的全面计算建模框架提供数据和见解
迁移中的代谢;项目2将额外提供肿瘤微泡用于功能评价。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jan Lammerding其他文献
Jan Lammerding的其他文献
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{{ truncateString('Jan Lammerding', 18)}}的其他基金
2022 Intermediate Filaments Gordon Research Conference and Seminar
2022年中间长丝戈登研究会议暨研讨会
- 批准号:
10469043 - 财政年份:2022
- 资助金额:
$ 38.26万 - 项目类别:
Nuclear mechanobiology in confined migration (Equipment Supplement 2023)
受限迁移中的核力学生物学(设备增刊2023)
- 批准号:
10796133 - 财政年份:2020
- 资助金额:
$ 38.26万 - 项目类别:
Nuclear mechanics and mechanotransduction in muscular laminopathies
肌肉核纤层蛋白病的核力学和机械转导
- 批准号:
8413555 - 财政年份:2007
- 资助金额:
$ 38.26万 - 项目类别:
Nuclear mechanics and mechanotransduction in muscular laminopathies
肌肉核纤层蛋白病的核力学和机械转导
- 批准号:
9067464 - 财政年份:2007
- 资助金额:
$ 38.26万 - 项目类别:
Nuclear mechanics and mechanotransduction in muscular laminopathies
肌肉核纤层蛋白病的核力学和机械转导
- 批准号:
7196846 - 财政年份:2007
- 资助金额:
$ 38.26万 - 项目类别:
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