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

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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.