IGF-I secretion by prostate carcinoma cells does not alter tumor-bone cell interactions in vitro or in vivo.
BACKGROUND
IGF-I is an important growth and differentiative factor for osteoblasts and may have a role in defining prostate cancer risk and skeletal metastases.


METHODS
Conditioned media (CM) from human prostate cancer (PC), C4-2 and C4-2B, which produce osteoblastic lesions, and PC-3, which causes osteolysis, was added to MC3T3-E1 bone cultures. SCID mice were injected intratibially with these engineered cells. Tumor bearing tibiae were analyzed by microCT and pQCT.


RESULTS
CM from PC cells increased osteoblast proliferation and differentiation and was unaltered by the type of PC cell, IGF-I antibodies, or exogenous IGF-I and IGFBP2. Study of intratibial PC tumors in SCID mice showed that C4-2 cells grew slowly preserving bone structure, while PC-3 tumors caused rapid osteolysis. Overexpression of IGF-I did not change either tumor progression or skeletal response.


CONCLUSIONS
IGF-I is neither necessary nor sufficient for the osteoblastic response to PC metastases.
Rubin
Janet
J
Department of Medicine, Emory University & VAMC, Decatur, Georgia.
Fan
Xian
X
Rahnert
Jill
J
Sen
Buer
B
Hsieh
Chia-Ling
CL
Murphy
Tamara C
TC
Nanes
Mark S
MS
Horton
Lindsay G
LG
Beamer
Wesley G
WG
Rosen
Clifford J
CJ
D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000556:secondary*; D002450:Cell Communication; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000737:chemistry; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000503:physiopathology; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology; D010014:Osteolysis / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013977:Tibia
D017077:Culture Media, Conditioned; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I