PMID- 10344214
OWN - NLM
STAT- MEDLINE
DCOM- 19990604
LR  - 20190915
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 39
IP  - 4
DP  - 1999 Jun 1
TI  - Osteomimetic properties of prostate cancer cells: a hypothesis supporting the 
      predilection of prostate cancer metastasis and growth in the bone environment.
PG  - 246-61
AB  - BACKGROUND: Unlike most other malignancies, prostate cancer metastasizes 
      preferentially to the skeleton and elicits osteoblastic reactions. METHODS: We 
      present a hypothesis, based upon results obtained from our laboratory and others, 
      on the nature of progression of prostate cancer cells and their predilection to 
      growth and metastasis in the bone microenvironment. We propose the hypothesis 
      that osseous metastatic prostate cancer cells must be osteomimetic in order to 
      metastasize, grow, and survive in the skeleton. The reciprocal interaction 
      between prostate cancer and bone stromal growth factors, including basic 
      fibroblast growth factor (bFGF), hepatocyte growth factor/scatter factor 
      (HGF/SF), and especially the insulin growth factor (IGF) axis initiates bone 
      tropism, and is enhanced by prostate secreted endothelin-1 (ET-1) and 
      urokinase-type plasminogen activator (uPA). Growth factors and peptides that have 
      differentiating activity, such as transforming growth factor beta (TGF-beta), 
      parathyroid hormone-related protein (PTH-rp), and the bone morphogenetic proteins 
      (BMPs), can shift local homeostasis to produce the characteristic blastic 
      phenotype, via interaction with prostate-secreted human kalikrein 2 (hK2), and 
      prostate-specific antigen (PSA). This proposal asserts that altering the 
      expression of certain critical transcription factors, such as Cbfa and MSX in 
      prostate cancer cells, which presumably are under the inductive influences of 
      prostate or bone stromal cells, can confer profiles of gene expression, such as 
      osteopontin (OPN), osteocalcin (OC), and bone sialoprotein (BSP), that mimic that 
      of osteoblasts. RESULTS AND CONCLUSIONS: Elucidation of common proteins, 
      presumably driven by the same promoters, expressed by both prostate cancer and 
      bone stromal cells, could result in the development of novel preventive and 
      therapeutic strategies for the treatment of prostate cancer skeletal metastasis. 
      Agents developed using these strategies could have the potential advantage of 
      interfering with growth and enhancing apoptosis in both prostate cancer and bone 
      stromal compartments. The selective application of gene therapy strategy, driven 
      by tissue-specific and tumor-restricted promoters for the safe delivery and 
      expression of therapeutic genes in experimental models of prostate cancer 
      metastasis, is discussed.
FAU - Koeneman, K S
AU  - Koeneman KS
AD  - Department of Urology, University of Virginia Health Sciences Center, 
      Charlottesville 22908, USA.
FAU - Yeung, F
AU  - Yeung F
FAU - Chung, L W
AU  - Chung LW
LA  - eng
GR  - CA63341/CA/NCI NIH HHS/United States
GR  - 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, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Growth Substances)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Bone Neoplasms/*metabolism/*secondary/therapy
MH  - Cell Division
MH  - Cell Transformation, Neoplastic
MH  - Gene Expression Regulation, Neoplastic
MH  - Growth Substances/metabolism
MH  - Humans
MH  - Male
MH  - Neoplasm Proteins/metabolism
MH  - Osteoblasts/metabolism/pathology
MH  - Phenotype
MH  - Prostatic Neoplasms/*metabolism/*pathology/therapy
RF  - 153
EDAT- 1999/05/27 06:00
MHDA- 2000/06/20 09:00
CRDT- 1999/05/27 06:00
PHST- 1999/05/27 06:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/05/27 06:00 [entrez]
AID - 10.1002/(SICI)1097-0045(19990601)39:4<246::AID-PROS5>3.0.CO;2-U [pii]
AID - 10.1002/(sici)1097-0045(19990601)39:4<246::aid-pros5>3.0.co;2-u [doi]
PST - ppublish
SO  - Prostate. 1999 Jun 1;39(4):246-61. doi: 
      10.1002/(sici)1097-0045(19990601)39:4<246::aid-pros5>3.0.co;2-u.