Project 2: Cellular topography and function of the breast cancer tissue microenvironment
项目2:乳腺癌组织微环境的细胞形态和功能
基本信息
- 批准号:10272390
- 负责人:
- 金额:$ 26.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-14 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:2-Oxoglutarate 5-Dioxygenase Procollagen-LysineAntibodiesArchivesAutomobile DrivingAvidityBiopsyBreast cancer metastasisCRISPR interferenceCell CommunicationCellsClinicalCollagenDataData SetDeaminaseDisease ProgressionDistantEnzymesEstrogen receptor positiveExcisionExtracellular MatrixFamilyFibroblastsFrequenciesHydroxylationImageImmuneImmune EvasionImmunosuppressionLabelLibrariesLocationMachine LearningMapsMass Spectrum AnalysisMetabolicMetalsMetastatic breast cancerMetastatic toMethodsMixed Function OxygenasesModelingModificationMolecularMorphologyMultiplexed Ion Beam ImagingNeighborhoodsNeoplasm MetastasisNivolumabNormal tissue morphologyOperative Surgical ProceduresOrganoidsOutcomePathogenesisPatientsPeptide HydrolasesPeptidesPlayPolysaccharidesPopulationProcessProcollagen-Proline DioxygenaseProtein GlycosylationProteinsProteomicsResolutionResourcesRiskRoleSamplingSiteSpecimenSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStainsStromal CellsStructural ProteinStructureTestingTherapeuticTimeTissue SampleTissue imagingTissuesTumor Cell MigrationWorkbiobankbreast cancer progressionbreast imagingcell typeclinically significantcollagenasecrosslinkglycosylationglycosyltransferasehigh riskimaging modalityimmune activationmacrophagemalignant breast neoplasmneoplastic cellpreventreceptorrecruitresponsetooltranscriptomicstriple-negative invasive breast carcinomatumortumor microenvironment
项目摘要
Abstract/Project Summary
Breast cancer (BC) metastasis is an emergent feature that occurs when the tumor’s ability to recruit metabolic
resources, avoid immune activation, and disseminate to distant sites exceeds the capacity of surrounding normal
tissue to prevent these processes. In line with this, work over the last decade has demonstrated the crucial role
played by the tumor microenvironment (TME) in promoting or deterring BC progression. Tumor cell migration
and immune recruitment have both been shown to be heavily influenced by fibroblasts and the surrounding
extracellular matrix (ECM) they produce. Additionally, protein glycosylation has been shown to modulate these
interactions. To understand how tumor glycosylation and ECM remodeling interact to potentiate BC metastasis,
we will use spatial transcriptomics and two complementary mass spectrometry methods, MIBI-TOF and MALDI,
to identify glycan-dependent, cell-cell, and cell-ECM interactions that shift the TME toward tumor permissive
states. All three analyses will be performed on spatially-coregistered serial sections from the same tissue blocks.
In doing so, comprehensive single-cell maps of each tissue sample constructed by MIBI-TOF can be directly
superimposed with de novo proteomic and transcriptomic data. We will map and enumerate the lineage and
major functional subsets of tumor and stromal cells with respect to relevant therapeutic and molecular
parameters to understand how the BC TME evolves with disease progression. These features will be overlaid
with de novo imaging of tissue glycans to identify potential mechanisms of immune evasion that involve tumor
sialoglycans and macrophage-bound SIGLECs. The frequency and spatial enrichment of these features will be
correlated with spatial transcriptomics data to identify regulatory glycosyltransferases promoting these
interactions. Next, ECM-MALDI and MIBI-TOF data will be used to identify how collagen type, hydroxylation, and
crosslinking shift in coordination with the collagen structure and function of neighboring cell populations. In
particular, we will focus on understanding how the activity of two families of enzymes, prolyl and lysyl
hydroxylases, drive structural changes in the ECM that promote BC metastasis. The clinical significance of these
extracted cellular and molecular definitions of ECM remodeling will be assessed with respect to metastatic risk,
stage, and IC subtype. Taken together, this work will provide an unprecedented view into how TME structure
and cell-cell interactions between tumor and stroma relate to specific facets of the tumor ECM and glycome.
抽象/项目总结
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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Robert michael Angelo其他文献
Robert michael Angelo的其他文献
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{{ truncateString('Robert michael Angelo', 18)}}的其他基金
Multimodal histologic atlas of human bone marrow
人骨髓多模态组织学图谱
- 批准号:
10531005 - 财政年份:2022
- 资助金额:
$ 26.33万 - 项目类别:
Multimodal histologic atlas of human bone marrow
人骨髓多模态组织学图谱
- 批准号:
10924351 - 财政年份:2022
- 资助金额:
$ 26.33万 - 项目类别:
Multimodal histologic atlas of human bone marrow
人骨髓多模态组织学图谱
- 批准号:
10673893 - 财政年份:2022
- 资助金额:
$ 26.33万 - 项目类别:
Project 2: Cellular topography and function of the breast cancer tissue microenvironment
项目2:乳腺癌组织微环境的细胞形态和功能
- 批准号:
10704687 - 财政年份:2021
- 资助金额:
$ 26.33万 - 项目类别:
A robust platform for multiplexed, subcellular proteomic imaging in human tissue
用于人体组织多重亚细胞蛋白质组成像的强大平台
- 批准号:
9894465 - 财政年份:2019
- 资助金额:
$ 26.33万 - 项目类别:
A robust platform for multiplexed, subcellular proteomic imaging in human tissue
用于人体组织多重亚细胞蛋白质组成像的强大平台
- 批准号:
10247827 - 财政年份:2019
- 资助金额:
$ 26.33万 - 项目类别:
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
MIRIAD - 阿尔茨海默病恢复力的多重成像
- 批准号:
9974453 - 财政年份:2017
- 资助金额:
$ 26.33万 - 项目类别:
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease
MIRIAD - 阿尔茨海默病恢复力的多重成像
- 批准号:
9439172 - 财政年份:2017
- 资助金额:
$ 26.33万 - 项目类别:
The Phenotypic Landscape of Cognitive Decline as Revealed by Next-Generation Multiplexed Ion Beam Imaging
下一代多重离子束成像揭示认知衰退的表型景观
- 批准号:
9910356 - 财政年份:2017
- 资助金额:
$ 26.33万 - 项目类别:
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