DEVELOPMENT OF A HYDROGEL BASED PROSTATE TUMOR MODEL FOR CANCER CELL MIGRATION STUDIES

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2022-1-12

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Demirkaya, Damla

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Prostate cancer is the second most diagnosed cancer in men and relapse due to the metastasis of cancer cells is the main reason of the high number of deaths in prostate cancer patients. Thus, there is a growing need for a tumor model to study the prostate cancer metastasis. In this study, a 3D model consisting of two natural polymer hydrogels (methacrylated collagen and methacrylated hyaluronic acid) with tunable mechanical and chemical properties carrying spheroids of two different prostate cancer cell lines (PC-3 and LNCAP) was developed to compare the effect of microenvironment on the migration. Fibroblast cells were incorporated in the hydrogel blend to increase the rate of migration of cancer cells. Migration of cancer cells in hydrogels with different compositions in the presence and absence of fibroblasts was studied with confocal laser scanning microscopy. The cancer cells in high collagen containing hydrogel were elongated, and the presence of fibroblasts in the microenvironment promoted the migration of prostate cancer cells by mimicking the microenvironment of prostate cancer more closely than other models. Epithelial-mesenchymal transition (EMT), a precondition for metastasis enhances mobility by decreasing epithelial markers and increasing mesenchymal markers. The quantification of migration was achieved through determination of E-cadherin and vimentin expression, the EMT marker proteins, through their fluorescence intensities in the immunostained samples. It was shown that E-cadherin expression was downregulated while vimentin expression was upregulated in the presence of fibroblast cells in high collagen containing hydrogel model as an indicator of migration.

Subject Keywords

Prostate cancer, Collagen, Migration, Hydrogel, Hyaluronic Acid

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https://hdl.handle.net/11511/96288

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

D. Demirkaya, “DEVELOPMENT OF A HYDROGEL BASED PROSTATE TUMOR MODEL FOR CANCER CELL MIGRATION STUDIES,” M.S. - Master of Science, Middle East Technical University, 2022.