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Studying E-cadherin dynamics during extravasation and metastatic colonization

研究外渗和转移定植过程中 E-钙粘蛋白的动态

基本信息

批准号：
10831158
负责人：
ROGER D KAMM
金额：
$ 17.73万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
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：
2021-09-17 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10831158
关键词：
3-Dimensional Address Adhesions Adhesives Affect Basement membrane Biological Assay Blood Platelets Breast Melanoma Cell Communication Cell Death Cell Survival Cells Cessation of life Chromatin Chromatin Structure Circulation Complex Computer Analysis Cytoskeleton Dermis Disease Disseminated Malignant Neoplasm E-Cadherin Endothelium Environment Extracellular Matrix Extravasation Fibrin Gene Expression Genomics Goals Image In Vitro Individual Intervention Liver Malignant Neoplasms Measurement Mechanics Methods Microcirculation Modeling Molecular Neoplasm Circulating Cells Neoplasm Metastasis Nuclear Organ Organ Specificity Pathway interactions Phenotype Primary Neoplasm Probability Process Proliferating Property Resolution Role Site Stress Techniques Technology Therapeutic Thrombus Time Tissues Tumor Cell Invasion Vision Work cell behavior cell type computer studies coping experience experimental study hemodynamics in vitro Model in vivo insight intravital imaging metastatic process migration monolayer mortality neoplastic cell novel therapeutics prevent programs response shear stress stressor transcriptome transcriptomics triple-negative invasive breast carcinoma

项目摘要

Overall: PROJECT SUMMARY Metastatic disease is responsible for the vast majority of cancer mortality. Understanding of the fundamental mechanisms leading to metastatic cancer has been hampered by the need for models that replicate the step- wise metastatic process in vivo, yet are amenable to tight control and facilitate high-resolution, time-lapse imaging and quantitative analysis of cell behavior. Over the past decade, our team has developed in vivo and in vitro methods capable of simulating many steps of the metastatic cascade including tumor cell invasion, intravasation, trapping in the microcirculation or adhesion to the vessel walls, and extravasation into the surrounding extracellular matrix. In parallel, we have developed computational studies that provided detailed insights often not possible through experiments. This collective prior work has shed new light on central aspects of single-cell and collective cell behavior during metastasis, and identified mechanical adaptations and vulnerabilities of the tumor cell with promise for targeted interventions. The goal of our proposed U54 Center is to employ these developed assays and methods in combination with new measurement techniques to interrogate the full spectrum of stressors experienced by tumor cells in the metastatic niche during arrest and extravasation, and couple these with parallel studies of changes in chromatin structure and the transcriptome of tumor cells (Core B). These changes are critical to mechano-adaptation of the tumor cells towards an organ-preferential initiation of a metastatic colony or transition to dormancy. A hallmark of our proposed center is the use of state- of-the-art in vitro (Project 1) and in vivo (Project 2) experiments and computation (Core A) to uncover and probe the factors that ultimately determine tumor cell fate. We anticipate that such integrated studies will provide new insights into metastatic cancer, not possible by the use of any method alone, and enhance our ability to identify and screen for new therapies to inhibit the tendency for metastatic spread of disease.

总体：项目总结

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.

DOI：
10.1002/advs.202206554
发表时间：
2023-06
期刊：
ADVANCED SCIENCE
影响因子：
15.1
作者：
Javanmardi, Yousef;Agrawal, Ayushi;Malandrino, Andrea;Lasli, Soufian;Chen, Michelle;Shahreza, Somayeh;Serwinski, Bianca;Cammoun, Leila;Li, Ran;Jorfi, Mehdi;Djordjevic, Boris;Szita, Nicolas;Spill, Fabian;Bertazzo, Sergio;Sheridan, Graham K.;Shenoy, Vivek;Calvo, Fernando;Kamm, Roger;Moeendarbary, Emad
通讯作者：
Moeendarbary, Emad

KRAS silencing impacts chromatin organization and transcriptional activity in colorectal cancer cells.

KRAS 沉默影响结直肠癌细胞的染色质组织和转录活性。

DOI：
10.21203/rs.3.rs-3752760/v2
发表时间：
2024
期刊：
Research square
影响因子：
0
作者：
Martins,Flávia;Machado,AnaLuísa;Ribeiro,Andreia;Oliveira,SusanaMendonça;Carvalho,Joana;Matthiesen,Rune;Backman,Vadim;Velho,Sérgia
通讯作者：
Velho,Sérgia

Towards targeting of shared mechanisms of cancer metastasis and therapy resistance.

DOI：
10.1038/s41568-021-00427-0
发表时间：
2022-03
期刊：
Nature reviews. Cancer
影响因子：
0
作者：
通讯作者：

Cytoplasmic accumulation and plasma membrane association of anillin and Ect2 promote confined migration and invasion.

anillin 和 Ect2 的细胞质积累和质膜结合促进有限的迁移和侵袭。

DOI：
10.21203/rs.3.rs-3640969/v1
发表时间：
2024
期刊：
Research square
影响因子：
0
作者：
Tran,AveryT;Wisniewski,EmilyO;Mistriotis,Panagiotis;Stoletov,Konstantin;Parlani,Maria;Amitrano,Alice;Ifemembi,Brent;Lee,SeJong;Bera,Kaustav;Zhang,Yuqi;Tuntithavornwat,Soontorn;Afthinos,Alexandros;Kiepas,Alexander;Jamieson,Joh
通讯作者：
Jamieson,Joh

T cell-mediated additive cytotoxicity - death by multiple bullets.