A new murine model of osteoblastic/osteolytic lesions from human androgen-resistant prostate cancer.

[en] 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.

Research center :

Giga-Cancer - ULiège

Disciplines :

Oncology
Biochemistry, biophysics & molecular biology

Author, co-author :

Fradet, Anais

Sorel, Helene

Depalle, Baptiste

Serre, Claire Marie

Farlay, Delphine

Turtoi, Andrei ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Follet, Helene

Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire

Clezardin, Philippe

Bonnelye, Edith

Language :

English

Title :

A new murine model of osteoblastic/osteolytic lesions from human androgen-resistant prostate cancer.

Publication date :

2013

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science, United States - California

Volume :

Issue :

Pages :

e75092

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

CNRS - Centre National de la Recherche Scientifique [FR]
Ligue Régionale contre le Cancer
ARTP - Association pour la Recherche sur les Tumeurs de la Prostate [FR]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]

Available on ORBi :

since 11 April 2014

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