title: Imaging the effects of castration on bone turnover and hormone-independent prostate cancer colonization of bone.
abstract: BACKGROUND
  Tumor populations may selectively colonize bone that is being actively remodeled. In prostate cancer patients, androgen deprivation directly inhibits tumor growth initially, whilst induced bone loss may facilitate tumor colonization of bone by androgen-insensitive cells. We have tested this hypothesis using a xenograft model of early growth of prostate cancer in bone.
  
  
  METHODS
  PC3 cells transfected with Green fluorescent protein (GFP) were injected into castrated and non-castrated athymic mice via intrabial and intracardiac routes. In vivo tumor growth was monitored daily and animals sacrificed 6-9 days following initial GFP-based detection of tumors. Tumor bearing and contra-lateral non-tumor bearing tibias were analyzed extensively by micro-CT and histology/immunohistochemistry for the presence of tumor cells and the effects of tumor and/or castration on bone cells and bone structure evaluated.
  
  
  RESULTS
  GFP-positive tumors in bone were visible from 12 days post-injection following intratibial injection, allowing tumors <1 mm diameter to be monitored in live animals. Castration did not affect tumor frequency, tumor volume, or time to initial appearance of tumors injected via intratibial or intracardiac routes. Castration decreased trabecular bone volume in all mice. Significant tumor-induced suppression of numbers of osteoblasts, coupled with increased numbers of activated osteoclasts, was evident in both intact animals and castrated animals.
  
  
  CONCLUSIONS
  In vivo GFP imaging allows the detection of early tumor growth at intra-osseous sites. Castration induces bone loss, but PC3-GFP cells are also capable of inducing bone remodeling in intact animals at early time points, independently of pre-existing castration-induced alterations to bone.
authors: Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK. n.a.cross@shef.ac.uk
authors: N A
authors: NA
authors: Cross
authors: A
authors: A
authors: Fowles
authors: K
authors: K
authors: Reeves
authors: N
authors: N
authors: Jokonya
authors: K
authors: K
authors: Linton
authors: I
authors: I
authors: Holen
authors: F C
authors: FC
authors: Hamdy
authors: C L
authors: CL
authors: Eaton
mesh_terms: D000728:Androgens / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000556:secondary*; D016723:Bone Remodeling; D049452:Green Fluorescent Proteins; D006801:Humans; D049408:Luminescent Agents; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: D000728:Androgens; D049408:Luminescent Agents; D049452:Green Fluorescent Proteins