Prostate Cancer (PCa) is one of the most commonly diagnosed cancers, and has a high propensity to metastasise, especially to the bone. The cancer microenvironment is now known to greatly influence the morphology, behaviour, and drug resistance of cancer cells1 , hence the importance of studying them in a biologically relevant in vitro cell culture model. To this end, we have developed a cell co-culture model which encapsulates the bone microenvironment in both extracellular matrix (ECM) composition and structure, with the added benefit of the presence of bone stromal support cells. Investigating both isolated cultures of PC3 (PCa), HS5 (Bone stromal) and co-cultures of PC3 & HS5, we have characterised changes in the morphology, their respective invasion rates, as well as changes in key Epithelial-Mesenchymal Plasticity (EMP) proteins. Interestingly, when cultured with PC3 cells, HS5 cells were seen to re-express N-Cadherin, consistent with a more metastatic phenotype, which was mediated by PC3-excreted factors. We also present data to suggest that α6 and β1 integrin subunits mediate behavioural, morphological and protein expression associated with metastatic dissemination in both isolated and co-cultures. These results show that not only is it important to study PCa using a relevant 3D ECM mimetic, but that by using a relevant co-culture system to encapsulate potential cell-cell interactions that occur in in vivo situations, more informative data can be obtained.