Establishment and characterization of osseous prostate cancer models: intra-tibial injection of human prostate cancer cells.
BACKGROUND
To improve the therapy of advanced prostate cancer (CaP), it is critical to develop animal models that mimic CaP bone metastases. Unlike the human disease, CaP xenograft models rarely metastasize spontaneously to bone from the orthotopic site of primary tumor growth.


METHODS
Single-cell suspensions of LNCaP, PC-3, LuCaP 35, and LuCaP 23.1 CaP cells were injected directly into tibia of SCID mice. Immunohistochemistry and bone histomorphometrical analyses were performed to characterize these osseous-CaP models.


RESULTS
LuCaP 23.1 yields an osteoblastic response, LNCaP yields mixed lesions, and LuCaP 35 and PC-3 result in osteolytic responses. We have detected osteoprotegerin, RANK ligand, parathyroid hormone-related protein, and endothelin-1, proteins associated with bone growth and remodeling, in the CaP cells grown in the bone.


CONCLUSIONS
These animal models can be used to study biological interactions, pathways, and potential therapeutic targets, and also to evaluate new agents for treatment and prevention of CaP bone metastasis.
Corey
Eva
E
University of Washington, Department of Urology, Seattle, Washington 98195, USA. ecorey@u.washington.edu
Quinn
Janna E
JE
Bladou
Franck
F
Brown
Lisha G
LG
Roudier
Martine P
MP
Brown
Julie M
JM
Buhler
Kent R
KR
Vessella
Robert L
RL
D000818:Animals; D015519:Bone Density; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D016723:Bone Remodeling; D002352:Carrier Proteins / Q000032:analysis; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D011471:Prostatic Neoplasms / Q000473:pathology*; D011506:Proteins / Q000032:analysis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D013977:Tibia / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019332:Endothelin-1; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human