A new murine model of osteoblastic/osteolytic lesions from human androgen-resistant prostate cancer.
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Up to 80% of patients dying from prostate carcinoma have developed bone metastases that are incurable. Castration is commonly used to treat prostate cancer. Although the disease initially responds to androgen blockade strategies, it often becomes castration-resistant (CRPC for Castration Resistant Prostate Cancer). Most of the murine models of mixed lesions derived from prostate cancer cells are androgen sensitive. Thus, we established a new model of CRPC (androgen receptor (AR) negative) that causes mixed lesions in bone. METHODS: PC3 and its derived new cell clone PC3c cells were directly injected into the tibiae of SCID male mice. Tumor growth was analyzed by radiography and histology. Direct effects of conditioned medium of both cell lines were tested on osteoclasts, osteoblasts and osteocytes. RESULTS: We found that PC3c cells induced mixed lesions 10 weeks after intratibial injection. In vitro, PC3c conditioned medium was able to stimulate tartrate resistant acid phosphatase (TRAP)-positive osteoclasts. Osteoprotegerin (OPG) and endothelin-1 (ET1) were highly expressed by PC3c while dikkopf-1 (DKK1) expression was decreased. Finally, PC3c highly expressed bone associated markers osteopontin (OPN), Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP) and produced mineralized matrix in vitro in osteogenic conditions. CONCLUSIONS: We have established a new CRPC cell line as a useful system for modeling human metastatic prostate cancer which presents the mixed phenotype of bone metastases that is commonly observed in prostate cancer patients with advanced disease. This model will help to understand androgen-independent mechanisms involved in the progression of prostate cancer in bone and provides a preclinical model for testing the effects of new treatments for bone metastases.
Date Issued
2013-09-19
Date Acceptance
2013-08-08
Citation
PLOS One, 2013, 8 (9)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLOS One
Volume
8
Issue
9
Copyright Statement
: © 2013 Fradet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
PII: PONE-D-13-23448
Subjects
Animals
Bone Neoplasms
Bone Remodeling
Bone and Bones
Cell Line, Tumor
Collagen Type I
Disease Models, Animal
Gene Expression
Humans
Male
Mice
Orchiectomy
Osteoblasts
Osteolysis
Prostatic Neoplasms
Xenograft Model Antitumor Assays
Publication Status
Published
Article Number
e75092