Characterization of C4-2 prostate cancer bone metastases and their response to castration.
New well-characterized preclinical models of prostate cancer (CaP) bone metastases are needed to improve our understanding of the development of CaP-related bone disease in patients. Here we describe characterization of a model consisting of direct injection of C4-2 cells into tibias.


BACKGROUND
Prostate cancer (CaP) has a high proclivity to metastasize to bone. Development and characterization of preclinical models of CaP bone metastases are of high interest. The objective of this study was to characterize C4-2 bone metastases and their response to castration.


METHODS
Cell suspensions of C4-2, a subline of LNCaP, were injected directly into the tibias of intact male mice. In groups A (n = 7) and B (n = 5), animals were killed 3 and 8 weeks after injection of C4-2 cells, respectively. In group C (n = 7), animals were castrated 3 weeks after injection and killed 5 weeks after castration. Serum prostate-specific antigen (PSA) levels and bone mineral density (BMD) were measured, and bone histomorphometric analysis was performed.


RESULTS
C4-2 cells decreased BMD of the injected tibias by 36.1% and bone volume by 74.1% versus normal tibias. Castration caused a 32.3% drop in serum PSA (p = 0.0438), with a nadir at day 14, after which it began to rise again. Bone destruction in the tumorous tibias of castrated animals was decreased by 15.9% versus tumorous tibias of intact animals (p = 0.0392). However, BMD in the tumorous tibias of castrated mice was still lower than in normal tibias of intact animals. Castration also decreased BMD and bone volume in nontumorous tibias (p = 0.0406 and 0.0232, respectively).


CONCLUSIONS
The C4-2 model of bone metastasis recapitulates the response to androgen deprivation observed in CaP patients with bone metastases and is suitable for study of interactions between tumor and bone cells and evaluation of new therapeutic modalities.
Department of Urology, University of Washington, Seattle 98195, Washington, USA.
Jesco
J
Pfitzenmaier
Janna E
JE
Quinn
Austin M
AM
Odman
Jian
J
Zhang
Evan T
ET
Keller
Robert L
RL
Vessella
Eva
E
Corey
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000473:pathology*; D002369:Castration; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D013977:Tibia / Q000473:pathology; D013997:Time Factors
D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen