Abstract
The fibromuscular stroma of the prostate regulates normal epithelial differentiation and contributes to carcinogenesis in vivo. We developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells increased organoid formation and directed organoid morphology into a branched acini structure similar to what is observed in vivo. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Stroma-induced phenotypes were similar in all patients examined, yet they maintained inter-patient heterogeneity in the degree of response. Stromal cells expressed growth factors involved in epithelial differentiation, which was not observed in non-prostatic fibroblasts. Organoids derived from areas of prostate cancer maintained differential expression of alpha-methylacyl-CoA racemase and showed increased viability and passaging when co-cultured with stroma. The addition of stroma to epithelial cells in vitro improves the ability of organoids to recapitulate features of the tissue and enhances the viability of organoids.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 304-317 |
| Number of pages | 14 |
| Journal | iScience |
| Volume | 12 |
| DOIs | |
| State | Published - Feb 22 2019 |
Funding
We thank the UIC Biorespository members, Dr. Klara Valyi-Nagy and Alex Susma, and the urologists, Drs. Michael Abern, Daniel Moreira, and Simone Crivallero, for facilitation of the tissue acquisition for the primary cell cultures. We thank the UIC Urology patients for donating their tissue to research. We thank Ke Ma at the UIC Fluorescence Imaging Core for assisting with confocal. We thank Manny Alonso and Maria Sverdlov at the UIC Histology and Tissue Imaging Core for assisting with AMACR staining. We thank Julian Pachecho for his help with Celleste™ analysis. This work was funded, in part, by the Department of Defense Prostate Cancer Research Program Health Disparities Idea Award PC121923 (Nonn)and the UIC Center for Clinical and Translation Science Pre-doctoral Education for Clinical and Translational Scientists (PECTS)Program (Richards, McCray)and by the National Institutes of Health's National Cancer Institute, grant numbers U54CA202995, U54CA202997, and U54CA203000, known as the Chicago Health Equity Collaborative (L.N. A.B.M. M.M. C.V. and S.A.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense. Conceptualization, Z.R. G.S.P. S.A.A. and L.N.; Methodology, Z.R. J.M. and T.M.; Investigation, Z.R. J.M. T.M. J.T.M. J.G. and M.L.Z.; Resources, L.N.; Writing – original draft, Z.R. and L.N.; Writing – Review and editing, T.M. Z.R. L.N. C.V. S.A.A. G.S.P. A.B.M.; Visualization, Z.R. and J.M.; Supervision, L.N. G.S.P. C.V. A.B.M. S.A.A.; Funding acquisition, L.N. C.V. S.A.A. A.B.M, M.M. The authors declare no competing interests. We thank the UIC Biorespository members, Dr. Klara Valyi-Nagy and Alex Susma, and the urologists, Drs. Michael Abern, Daniel Moreira, and Simone Crivallero, for facilitation of the tissue acquisition for the primary cell cultures. We thank the UIC Urology patients for donating their tissue to research. We thank Ke Ma at the UIC Fluorescence Imaging Core for assisting with confocal. We thank Manny Alonso and Maria Sverdlov at the UIC Histology and Tissue Imaging Core for assisting with AMACR staining. We thank Julian Pachecho for his help with Celleste™ analysis. This work was funded, in part, by the Department of Defense Prostate Cancer Research Program Health Disparities Idea Award PC121923 (Nonn) and the UIC Center for Clinical and Translation Science Pre-doctoral Education for Clinical and Translational Scientists (PECTS) Program (Richards, McCray) and by the National Institutes of Health’s National Cancer Institute, grant numbers U54CA202995 , U54CA202997 , and U54CA203000 , known as the Chicago Health Equity Collaborative (L.N., A.B.M., M.M., C.V., and S.A.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense.
Keywords
- Bioengineering
- Biological Sciences
- Cell Biology
- Tissue Engineering
ASJC Scopus subject areas
- General
