A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread
Daniela Loessner, Simone C Rizzi, Kathryn S Stok, Tobias Fuehrmann, Brett Hollier, Viktor Magdolen, Dietmar W Hutmacher, Judith A Clements
Biomaterials | ELSEVIER SCI LTD | Published : 2013
Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevanc..View full abstract
The authors are grateful to Dr Deborah Stenzel, Dr Christina Theodoropoulos, and Dr Luke Nothdurft from the Analytical Electron Microscopy Facility of the Queensland University of Technology (QUT) for their assistance with the microscopy techniques. The authors thank Eva C Weber for her assistance with the immunohistochemistry. This study was supported by the National Health and Medical Research Council of Australia (D.L., D.W.H., and J.A.C); two Early Career Research Awards, Institute of Health and Biomedical Innovation, QUT, Australia (S.C.R., D.L.); a Smart State Fellowship of the Queensland Government, QUT (S.C.R.); and the German Federal Ministry of Education and Research, Leading Edge Cluster m4 (V.M.). Part of the research was funded by a mobility grant (Personlized Medicine) from the German Academic Exchange Service (DAAD) to D.L., V.M., D.W.H., and J.A.C.