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Characterization of relation between tissue viscoelasticity and tumor progression in aging tissues

衰老组织中组织粘弹性与肿瘤进展之间关系的表征

基本信息

批准号：
10302055
负责人：
Seungman Park
金额：
$ 15.09万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2021-09-15 至 2022-06-26
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10302055
关键词：
3-Dimensional Address Adipocytes Affect Age Aging Binding Biological Assay Biological Markers Biological Models Biophysics Cells Characteristics Chromatin Coin Collagen Collagen Fiber Cues Custom Dermis Development Devices Disease Epidermis Etiology Exhibits Extracellular Matrix Fibroblasts Fluorescence Recovery After Photobleaching Functional disorder Gene Expression Genetic Transcription Human Ice Immunoprecipitation In Situ In Vitro Incidence Individual Kinetics Knowledge Lead Link Longitudinal Studies MDM2 gene Malignant Neoplasms Mass Spectrum Analysis Measurement Measures Mechanics Mediating Modeling Modulus Molecular Mutation Pathology Pathway interactions Phenotype Polymers Relaxation Reporting Research Design Risk Factors Skin Skin Aging Skin Cancer Skin Tissue Squamous cell carcinoma Stress Subcutaneous Tissue TP53 gene Technology Testing Time Tissues Tumor Cell Invasion Tumor Suppressor Proteins Ubiquitin Western Blotting age effect age group age related base bioprinting cancer cell cell motility cost crosslink effective therapy fundamental research gain of function human subject in vitro Model in vivo keratinocyte mechanical properties mimetics mimicry mutant older patient portability senescence three-dimensional modeling tool tumor progression ubiquitin ligase ubiquitin-protein ligase viscoelasticity

项目摘要

PROJECT SUMMARY Though a number of studies have been reported regarding how aging-associated mutations lead to the higher incidence of cancer development and more aggressive cancer progression in elderly patients, few studies, if any, address that how altered mechanical characteristics of the microenvironment in aging tissues affect the course of cancer pathology. Mounting evidence strongly supports that mechanical properties of the tissues, including elastic modulus and relaxation time, significantly contribute to the pace of tumor progression. The reported results so far agree with the notion that the mechanical properties of aging tissues and cells are different from those of young tissues and cells. Given that tissues are, in general, stiffer in older individuals and tissue stiffness is known to promote tumor progression, we hypothesize that aging skin tissue, exhibiting distinct mechanical characteristics, promotes the progression of skin cancer in elderly patients via p53-mediated pathways. To prove this hypothesis, first, we plan to overcome the knowledge gap in the systematic quantification of the different mechanical properties between young and aging tissues. We will measure the elastic modulus and relaxation time of human skin tissues of different ages using a custom-built indentation-based mechanical analyzer. Second, to systematically investigate how the altered mechanical property promotes tumor progression, we will establish an in vitro model system in the mimicry of young and aging tissues. Third, we will use the in vitro model system to evaluate the rate of tumor progression, p53 abundance, stability and activity in skin cells growing in the varied mechanical/viscoelastic microenvironment.

项目总结