Prostate cancer (PCa) is one of the most common cancers affecting men and was estimated to be the second leading cause of cancer death for men in the US in 2019 (1).

Prostate cancer (PCa) is one of the most common cancers affecting men and was estimated to be the second leading cause of cancer death for men in the US in 2019 (1). This proposed project aims to develop three-dimensional (3D) collagen-based scaffold models suitable for the study of the epithelial to mesenchymal (EMT) process in prostate cancer. In particular, the work will assess the EMT process, an important step in metastatic progression, where epithelial cells acquire mesenchymal characteristics (2) and increased cellular plasticity, motility, drug resistance, and cancer stem cell features (3, 4), on two different scaffolds which have been developed in the TERG group: collagen-hyaluronic acid (CHyA) and collagen-chondroitin sulfate (CCS). As the prostate ECM is a 3D network composed of macromolecules, including collagen, proteoglycans, HyA, and CS (5), we hypothesise the investigation of prostate cancer cells on these highly relevant scaffold types will allow elucidation of the EMT process in a microenvironment that recapitulates the tumour microenvironment (TME). CCS scaffolds have previously been successfully used to culture prostate cancer cells and showed they were capable of supporting prostate cancer cell growth (6). ECM remodeling in the TME is often deregulated in cancer development and progression, and causes changes in ECM stiffness and composition that may promote cancer metastasis (7). ECM plays an important role in EMT [8], as periostin activates Snail through P-Akt pathway in PCa [9] and ECM stiffening cooperates with transforming growth factor beta (TGFβ) to induce breast cancer EMT [10]. The stiffness of the ECM increases during the malignant progression of cancer, promoting more aggressive and metastatic phenotypes in several cancers (11, 12) and therefore will be investigated in this study to determine the effect of three different scaffold stiffnesses on the different scaffold types on the EMT process in prostate cancer. Within the TERG group, we have developed the expertise and techniques to alter the stiffness of the scaffolds (13). Finally, the optimal biomimetic scaffolds will be used as novel platforms for the study of drug development and delivery with a focus on the EMT pathway.