Development of biomimetic 3D cancer platform for drug testing

• Main Author: Ker, Sia Fong
• Other Authors: Tan Lay Poh
• Format: Final Year Project
• Language: English
• Published: 2015
• Subjects: DRNTU::Engineering::Materials
• Online Access: http://hdl.handle.net/10356/62467
• Institution: Nanyang Technological University

Cancer accounts for most of the deaths in the world and it is mainly due to metastasis that makes treatment of cancer difficult. Epithelial-to-Mesenchymal Transition plays an important role in tumour metastasis as well as in tumour recurrence, the conversion of epithelial cells to mesenchymal cells can result in the acquisition of migratory and invasive properties. There are numerous studies on how stiffness of extracellular matrix, signals from the environment, type of extracellular matrix and the presence of integrins can affect cell behavior and migration. However, there are limited studies looking at how the physical and material characteristics of the microenvironment affect the Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition of highly invasive tumor cell lines. Conventional 2D cell culture models have also been proven to be inadequate in mimicking the environment of 3D native tissues. In response, a 3D culture model has been gradually gaining popularity among research groups due to its better representation of the microenvironment of living tissues. Therefore in this study, we propose a 3D biomimetic culture model constructed with 5% PEG 5% Gelatin matrix and collagen I matrix to study the EMT and MET transition in the human body environment. MDA-MB-231 cancer spheroids were then placed in the PEG + Gelatin matrix in a polyethylene terephthalate plastic construct before the addition of a collagen matrix layer at the top. From this study, we had found out that the design of the construct was suitable to mimic the EMT and MET phenomenon. However, there were a few limitations of the culture model. First, spheroids were not fully immersed in PEG + Gelatin matrix as they sunk into the collagen matrix when added. Also, the non-invading cancer cells in the spheroids facing the PEG + Gelatin matrix were suspected to have poor nutrient gradient and the inadequate presence of integrins in the matrix. Hence, future work or improvement to the 3D biomimetic culture model have to be done before we could fully understand whether EMT and MET of highly invasive tumor cell lines are critically determined by the physical and material characteristics of the microenvironment.