Human ex vivo 3D bone model recapitulates osteocyte response to metastatic prostate cancer
Abstract
Prostate cancer (PCa) is the second leading cause of cancer deaths among American men. Unfortunately, there is no cure once the tumor is established within the bone niche. Although osteocytes are master regulators of bone homeostasis and remodeling, their role in supporting PCa metastases remains poorly defined. This is largely due to a lack of suitable ex vivo models capable of recapitulating the physiological behavior of primary osteocytes. To address this need, we integrated an engineered bone tissue model formed by 3D-networked primary human osteocytes, with conditionally reprogrammed (CR) primary human PCa cells. CR PCa cells induced a significant increase in the expression of fibroblast growth factor 23 (FGF23) by osteocytes. The expression of the Wnt inhibitors sclerostin and dickkopf-1 (Dkk-1), exhibited contrasting trends, where sclerostin decreased while Dkk-1 increased. Furthermore, alkaline phosphatase (ALP) was induced with a concomitant increase in mineralization, consistent with the predominantly osteoblastic PCa-bone metastasis niche seen in patients. Lastly, we confirmed that traditional 2D culture failed to reproduce these key responses, making the use of our ex vivo engineered human 3D bone tissue an ideal platform for modeling PCa-bone interactions.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 19, 2018
- Source ID
- 10.1038/s41598-018-36424-x
Entities
People
- Christopher Albanese
- Ciaran Mannion
- Eugenia Dziopa
- Jenny Zilberberg
- Lucas Tricoli
- Poornema Ramasundaram
- Saba Choudhary
- Woo Lee
- Yair Kissin
Organizations
- Congressionally Directed Medical Research Programs
- National Cancer Institute
- National Institutes of Health
- National Science Foundation
- New Jersey Health Foundation