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

项目总结 尽管已经报道了一些关于衰老相关突变如何导致 老年患者癌症发展的发病率更高，癌症进展更具侵袭性，很少有研究， 如果有的话，阐述衰老组织中微环境机械特征改变如何影响 癌症病理学的病程。越来越多的证据有力地支持了组织的机械性能， 包括弹性模数和松弛时间在内，对肿瘤进展的速度有显著影响。这个 到目前为止，已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。考虑到组织通常在老年人和组织中更坚硬 僵硬是已知的促进肿瘤进展的因素，我们假设老化的皮肤组织，表现出明显的 机械特性，通过P53介导促进老年皮肤癌的进展 小路。为了证明这一假设，我们首先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不同的机械性能。我们将测量弹性模数 和松弛时间的不同年龄的人皮肤组织使用定制的压痕为基础的机械 分析器。第二，系统地研究改变的机械性能如何促进肿瘤 进展，我们将建立一个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.