title: Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model.
abstract: Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, QLD, Australia.
authors.forename: Shirly
authors.initials: S
authors.lastname: Sieh
authors.forename: Amy A
authors.initials: AA
authors.lastname: Lubik
authors.forename: Judith A
authors.initials: JA
authors.lastname: Clements
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009362:Neoplasm Metastasis; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger