PMID- 10898343
OWN - NLM
STAT- MEDLINE
DCOM- 20000727
LR  - 20190620
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 88
IP  - 12 Suppl
DP  - 2000 Jun 15
TI  - Establishment of human prostate carcinoma skeletal metastasis models.
PG  - 2995-3001
AB  - BACKGROUND: Prostate carcinoma progression from an androgen dependent (AD) state 
      to an androgen independent (AI) state occurs clinically in patients who undergo 
      hormonal therapy. In their laboratory, the authors developed two human prostate 
      carcinoma skeletal metastasis models, the LNCaP progression model and the ARCaP 
      model, to investigate phenotypic and genotypic changes of prostate carcinoma 
      cells during disease progression and to understand molecular pathways for 
      potential therapeutic targeting. METHODS: LNCaP or ARCaP cells were inoculated in 
      athymic mice and were exposed to selective hormonal conditions both in vivo and 
      in vitro. The effects of various hormonal treatment regimens on tumor volumes and 
      distant metastasis and the effects of bone stromal cells on prostate specific 
      antigen (PSA) expression by prostate carcinoma cells were evaluated. RESULTS: The 
      authors propose that prostate carcinoma progression from the AD state to the AI 
      state assumes three AI phenotypes: AI that remains androgen responsive, AI that 
      is unresponsive to androgen stimulation, and AI that is suppressed by or 
      hypersensitive to androgen. AI prostate carcinoma cells interacted reciprocally 
      with osteoblasts to produce enhanced tumor growth and osteoblastic reaction when 
      they are deposited in bone. Bone stromal cell conditioned media stimulated 
      prostate carcinoma cell growth and suppressed its PSA expression, as also 
      evidenced by androgen receptor-mediated transactivation of PSA promoter reporter 
      activity. Conditioned media obtained from prostate carcinoma cells also 
      stimulated osteoblastic cell growth in vitro. A novel gene therapy strategy is 
      being developed to target prostatic tumor epithelium and its supporting stroma 
      using tissue specific and tumor-restricted, promoter-directed toxic gene 
      expression in both cellular compartments. In addition, new strategies are being 
      designed to target the tumor endothelial system in the stroma and tumor 
      cell-extracellular matrix interaction mediated by isotype specific integrins. 
      CONCLUSIONS: Prostate carcinoma skeletal metastasis models may prove useful in 
      developing a new targeting strategy for the prevention and treatment of patients 
      with prostate carcinoma.
FAU - Zhau, H E
AU  - Zhau HE
AD  - Department of Urology, University of Virginia Health System, Charlottesville 
      22908, USA.
FAU - Li, C L
AU  - Li CL
FAU - Chung, L W
AU  - Chung LW
LA  - eng
GR  - CA6334/CA/NCI NIH HHS/United States
GR  - CA76620/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/*secondary
MH  - *Disease Models, Animal
MH  - Humans
MH  - Male
MH  - Mice
MH  - Prostatic Neoplasms/*pathology/therapy
RF  - 42
EDAT- 2000/07/18 11:00
MHDA- 2000/08/01 11:00
CRDT- 2000/07/18 11:00
PHST- 2000/07/18 11:00 [pubmed]
PHST- 2000/08/01 11:00 [medline]
PHST- 2000/07/18 11:00 [entrez]
AID - 10.1002/1097-0142(20000615)88:12+<2995::AID-CNCR15>3.0.CO;2-Y [pii]
AID - 10.1002/1097-0142(20000615)88:12+<2995::aid-cncr15>3.3.co;2-p [doi]
PST - ppublish
SO  - Cancer. 2000 Jun 15;88(12 Suppl):2995-3001. doi: 
      10.1002/1097-0142(20000615)88:12+<2995::aid-cncr15>3.3.co;2-p.