An In Vitro 3D Model to Evaluate Behaviour of Breast Cancer Cells and Response to Treatment

Azimi, T. 2019. An In Vitro 3D Model to Evaluate Behaviour of Breast Cancer Cells and Response to Treatment. PhD thesis University of Westminster Life Sciences

TitleAn In Vitro 3D Model to Evaluate Behaviour of Breast Cancer Cells and Response to Treatment
TypePhD thesis
AuthorsAzimi, T.
Abstract

The field of 3D culture models of disease has started to move towards systems that aim to recapitulate the complexity of human tissues. However, despite recent improvements, current 3D systems remain overly simplistic, lacking the biophysical characteristics and diverse structures found in most organs.
In this project, the cellular behaviour of breast cancer and their responsiveness to chemotherapeutic agents were evaluated under different 3D cell culture conditions. MDA-MB231 and SKBR3 cells were prepared as spheroids using ultra-low attachment plates and as 'artificial cancer masses' (ACM) by embedding cells in a dense collagen type-I. The ACMs were maintained under flow (150 μL/min) and flow/pressure (550 μL/min, ~19 mmHg) conditions. A significant reduction in cell viability was observed when cancer cells were grown as ACM compared to 2D culture. Cell viability also declined significantly when ACMs were maintained in flow/pressure condition compared to static condition. Similarly, an increase in the expression levels of markers of EMT was observed when cells were cultured as ACM. However, compared to static 3D incorporation of flow and pressure was associated with decreased expression levels of vimentin, HIF1-α, whilst MMP14 expression increased and snail remained unchanged. HER2 levels were increased in SKBR3 when the cells were cultured under flow/pressure (1.5 fold) compared to static condition. Overall, cells cultured as ACMs exhibited reduced responsiveness to doxorubicin compared to those grown in the conventional 2D culture. A decrease sensitivity was also observed in 3D/flow/pressure and 3D/flow compared to 3D/static condition.
The results obtained in this study show that cancer cell behaviour and their response to therapeutic agents are affected by different microenvironments. Therefore, a new generation of 3D in vitro models need to be developed as pre-clinical drug testing platforms.

Year2019
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