Chemo-Mechanical Feedback between CAFs, Leader Cells, and the Extracellular Microenvironment Regulates Leader Cell Regulated Collective Cell Migration
CAF、前导细胞和细胞外微环境之间的化学机械反馈调节前导细胞调节集体细胞迁移
基本信息
- 批准号:10537168
- 负责人:
- 金额:$ 6.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAdhesionsAffectAmericanAttentionBiochemicalBiologicalBiological AssayBiological ProcessBiomechanicsBreast Cancer CellBreast cancer metastasisCancerousCell AdhesionCell physiologyCellsCessation of lifeChemical ModelsChemicalsCollagenCollagen FiberCollagen ReceptorsCoupledCouplingDataDevicesDiagnosisEngineeringEnvironmentExperimental DesignsExtracellular MatrixFeedbackFibrillar CollagenFibroblastsGoalsHeterogeneityHumanImageIntegrin BindingLab-On-A-ChipsMalignant NeoplasmsMammary NeoplasmsMeasuresMechanicsMetastatic breast cancerMicrofluidic MicrochipsMicrofluidicsModelingMusNeoplasm MetastasisNormal tissue morphologyOrganOrganoidsPlayPredictive Cancer ModelPrimary NeoplasmProteomicsRecombinant ProteinsResearch ProposalsRoleSignal TransductionStromal CellsStromal NeoplasmStructureTechniquesTestingTissuesTumor Cell InvasionTumor Cell LineUnited StatesWomanadhesion receptorbasecancer cellcancer diagnosiscancer therapycell motilitydesigndiscoidin receptorextracellularflexibilitygenetic manipulationin vivoineffective therapieslive cell imagingmalignant breast neoplasmmammarymechanical forcemechanical signalmigrationmortalityneoplastic cellnovelpreventreconstitutionsecond harmonicsingle-cell RNA sequencingtargeted cancer therapytherapeutic targettranslational impacttumortumor microenvironment
项目摘要
Project Summary/Abstract
The impact of cancer associated fibroblasts (CAFs) and the extracellular microenvironment (ECM) in cancer
metastasis has become more and more appreciated. The tumor microenvironment consists of multiple
compartments: cellular, physical, and chemical. Each compartment in cancerous tissues differs greatly from
normal tissue, yet the role that each plays in metastasis and how they affect each other is poorly understood.
CAFs have been shown to promote tumor cell metastasis in part by altering the local collagen
microenvironment. CAFs can enhance cancer metastasis in 3 ways; (1) direct association between CAFs and
leader cells within the tumor, (2) CAF mechanical alterations of the local microenvironment, and (3) CAF
secretions that can signal for tumor metastasis and collagen remodeling. How the chemo-mechanical feedback
between CAFs, cancer cells, and the ECM remains poorly understood. Here, our goal is to elucidate the
chemo-mechanical feedback function of CAFs on leader cells and the microenvironment that facilitates
directed collective cell migration. (1) Quantify the impact of CAFs on collective cell migration and ECM
remodeling. (2) To examine the effect of the CAF secretome on local collagen structure and function. We will
utilize microfluidic cell-based invasion assays in conjunction with primary breast tumor organoids or
reconstituted breast tumor organoids (non-migratory mammary cells mixed with isolated leader cells or CAFs)
to probe the effect of CAFs on collective cell migration. We will isolate the role of mechanical forces generated
by CAFs within the tumor on leader cell function and the effect of CAF generated forces on collagen
deformation and remodeling (1). We will then compare the mechanical effect of CAFs on collective migration to
that of the chemical CAF secretions on collagen remodeling (2). We aim to quantify the relative role of both
mechanical and chemical models to generate a predictive model of CAF function on collective cell migration.
We will verify this model by using engineering techniques to manipulate the microenvironment and observe the
effect on collective migration. We will combine this with biological techniques to genetically manipulate CAFs
and leader cells to identify how CAFs are capable of effecting collective cell migration.
项目总结/文摘
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Vasilios Aris Morikis其他文献
Vasilios Aris Morikis的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 6.98万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 6.98万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 6.98万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 6.98万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 6.98万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 6.98万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 6.98万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 6.98万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 6.98万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 6.98万 - 项目类别:














{{item.name}}会员




