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

项目摘要 尽管已经报道了一些关于衰老相关突变如何导致 老年患者中癌症发生率更高，癌症进展更具侵袭性，很少有研究， 如果有的话，解决了老化组织中微环境的机械特性改变如何影响 癌症病理学课程。越来越多的证据有力地支持了组织的机械特性， 包括弹性模量和弛豫时间，对肿瘤进展的速度有显著贡献。的 到目前为止，报道的结果与衰老组织和细胞的机械性能不同的观点一致 从年轻的组织和细胞中分离出来一般来说，老年人的组织更硬， 僵硬是已知的，以促进肿瘤的进展，我们假设老化的皮肤组织，表现出不同的， 机械特性，通过p53介导促进老年患者皮肤癌的进展 途径。为了证明这一假设，首先，我们计划克服系统量化中的知识鸿沟 年轻组织和衰老组织之间的不同机械性能。我们将测量弹性模量 使用定制的基于压痕的机械装置， 分析仪第二，系统地研究力学性质的改变如何促进肿瘤的发生， 随着研究的深入，我们将建立一个模拟年轻和衰老组织的体外模型系统。三是 使用体外模型系统评估肿瘤进展速率、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。

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.