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Title: Low frequency shear waves as a potential mechanotherapy approach in cancer
Author: Glatz, Marlies
ISNI:       0000 0004 7970 080X
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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According to the World Health Organisation (WHO), cancer is the second leading cause of death globally, with almost every 6th death being due to cancer. Key hallmarks of cancer include uncontrolled cell growth, invasion into the surrounding tissue and metastasis to other organs, with metastasis known to be the cause of 90% of cancer-related deaths. Cells within the tissue microenvironment integrate both biochemical and physical signals to maintain homeostasis. Mechanical forces have been shown to affect many aspects of normal and tumour cell behaviour. Previous work showed that mechanical forces (stresses), displacements (shear) and deformations could be translated into biochemical signals, thereby affecting cancer cell survival. The goal of this project was to evaluate in cells a novel non-invasive therapeutic approach targeting cancer cell growth and invasion by inducing focused shear waves. The first aim was to design a device able to precisely move 3D-cultured cells continuously in a unilateral direction, whilst resisting temperature and humidity encountered in tissue culture incubators over long periods of time. Shear wave simulations were used to identify the maximum shear strain within the cell cultures. The integrity and mechanical shear properties of the 3D matrix, a bovine collagen type 1 gel, were measured via magnetic resonance elastography and second harmonic-generation multi-photon microscopy. The second aim was to create an in vitro 3D assay to observe changes in growth and invasion of cancer cells when exposed to low frequency shear waves at different amplitudes. Tumour spheroids were formed from metastatic human breast cancer cells and embedded in bovine collagen type 1 matrices. We showed that by keeping the frequency constant and altering the amplitude, three different outcomes are possible. First, a low amplitude was shown to increase cancer cell growth and invasion into the matrix compared to control cells, which underwent no treatment. Second, for an intermediate amplitude no significant differences were observed between shaken and control cells' behaviour. Third, using a high amplitude, a reduction in tumour growth and invasive behaviour was seen. This project demonstrates, that exposing a tumour spheroid multiple times to low frequency shear strain causes different effects on cell growth and invasive behaviour depending on the applied displacement. These results provide a first insight into the potential use of shear waves as a therapeutic approach.
Supervisor: Sinkus, Ralph Roman ; Fruhwirth, Gilbert Otto Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available