PMID- 9436028
OWN - NLM
STAT- MEDLINE
DCOM- 19980224
LR  - 20131121
IS  - 0018-1994 (Print)
IS  - 0018-1994 (Linking)
VI  - 43
IP  - 11
DP  - 1997 Nov
TI  - Human prostate cancer progression models and therapeutic intervention.
PG  - 815-20
AB  - Our laboratory has developed two cellular models of human prostate cancer 
      progression. The LNCaP prostate cancer progression model is based upon the 
      well-known cellular interaction between human prostate or bone stromal cells and 
      LNCaP cells in vivo. The marginally tumorigenic LNCaP cells acquired tumorigenic 
      and metastatic potential upon cellular interaction with either prostate or bone 
      fibroblasts. A subline termed C4-2 was observed to grow readily in castrated 
      animals and acquired metastatic potential spreading from the primary tumor site 
      to the lymph node, the seminal vesicles, and the axial skeleton, resulting in an 
      intense osteoblastic reaction. The second model is ARCaP, where prostate cancer 
      cells derived from the ascites fluid of a man with metastatic disease exhibited 
      an Androgen- and estrogen-Repressed Prostate Cancer cell growth and tumor 
      formation in either a hormone-deficient or a castrated environment. However, the 
      growth of either the tumor cells in vitro or the tumors in vivo was suppressed by 
      both estrogen and androgen. While the tumor cells expressed low levels of 
      androgen receptor and prostate-specific antigen (PSA), they were highly 
      metastatic when inoculated orthotopically. Distant metastases to a number of 
      organs were detected, including the liver, lung, kidney, and bone. We have 
      employed a human prostate cancer progression model as a system to study the 
      efficacy of gene therapy. Results of the study show that whereas universal 
      promoters, such as Cytomegalovirus (CMV) and Rous Sarcoma Virus (RSV) 
      promoter-driven tumor suppressors (e.g. p53, p21, and p16), were effective in 
      inhibiting prostate tumor growth, the advantages of driving the expression of 
      therapeutic toxic genes using a tissue-specific promoter prostate-specific 
      antigen (PSA) and a tumor--but not tissue-specific promoter, osteocalcin (OC), 
      are preferred. In the case of the PSA promoter, we can achieve cell-kill in 
      PSA-producing human prostate cancer cells. To circumvent the supporting role of 
      bone stroma for prostate cancer epithelial growth, we have recently developed a 
      novel concept where the expression of therapeutic toxic genes is driven by a 
      tumor--but not a tissue-specific OC promoter. Osteocalcin-thymidine kinase 
      (OC-TK) was found to efficiently eradicate the growth of osteosarcoma, prostate, 
      and brain tumors both in vitro and in vivo. We observed that androgen-independent 
      human prostate cancer cells lines expressed OC-TK at higher levels than 
      androgen-dependent human prostate cancer cell lines. We have obtained data to 
      suggest that Ad-OC-TK plus a pro-drug acyclovir (ACV) may be used as an effective 
      therapy to treat prostate cancer bone metastasis in models where the growth of 
      androgen-independent PC-3 and C4-2 tumors in the bone has occurred.
FAU - Chung, L W
AU  - Chung LW
AD  - Department of Urology, University of Virginia Health Sciences Center, 
      Charlottesville, USA.
FAU - Kao, C
AU  - Kao C
FAU - Sikes, R A
AU  - Sikes RA
FAU - Zhau, H E
AU  - Zhau HE
LA  - eng
GR  - R01 CA64863/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Japan
TA  - Hinyokika Kiyo
JT  - Hinyokika kiyo. Acta urologica Japonica
JID - 0421145
RN  - 0 (Androgens)
RN  - 0 (Prodrugs)
RN  - 104982-03-8 (Osteocalcin)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - X4HES1O11F (Acyclovir)
SB  - IM
MH  - Acyclovir/therapeutic use
MH  - Androgens/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - *Genetic Therapy
MH  - Humans
MH  - Male
MH  - Osteocalcin/genetics/therapeutic use
MH  - Prodrugs/therapeutic use
MH  - Promoter Regions, Genetic
MH  - Prostate-Specific Antigen/genetics
MH  - *Prostatic Neoplasms/pathology/therapy
MH  - Thymidine Kinase/therapeutic use
MH  - Tumor Cells, Cultured
RF  - 12
EDAT- 1998/01/22 00:00
MHDA- 1998/01/22 00:01
CRDT- 1998/01/22 00:00
PHST- 1998/01/22 00:00 [pubmed]
PHST- 1998/01/22 00:01 [medline]
PHST- 1998/01/22 00:00 [entrez]
PST - ppublish
SO  - Hinyokika Kiyo. 1997 Nov;43(11):815-20.