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.

项目概要尽管已经报道了许多关于与衰老相关的突变如何导致老年患者癌症发生率较高且癌症进展更具侵袭性，但很少有研究，如果有的话，请说明老化组织中微环境的机械特性改变如何影响癌症病理学过程。越来越多的证据强烈支持组织的机械特性，包括弹性模量和松弛时间，对肿瘤进展的速度有显着贡献。这迄今为止报道的结果同意衰老组织和细胞的机械性能不同的观点来自年轻组织和细胞的那些。考虑到老年人的组织通常更僵硬，并且组织众所周知，僵硬会促进肿瘤进展，我们假设老化的皮肤组织表现出明显的机械特性，通过 p53 介导促进老年患者皮肤癌的进展途径。为了证明这个假设，首先，我们计划克服系统量化方面的知识差距年轻组织和衰老组织之间不同的机械性能。我们将测量弹性模量使用定制的基于压痕的机械装置测量不同年龄的人体皮肤组织的松弛时间分析仪。其次，系统地研究机械性能的改变如何促进肿瘤的发生随着进展，我们将建立模拟年轻和衰老组织的体外模型系统。第三，我们将使用体外模型系统评估肿瘤进展速度、p53丰度、稳定性和活性皮肤细胞在不同的机械/粘弹性微环境中生长。