PMID- 25278011
OWN - NLM
STAT- MEDLINE
DCOM- 20160412
LR  - 20220311
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 12
DP  - 2014 Oct 3
TI  - PCSD1, a new patient-derived model of bone metastatic prostate cancer, is 
      castrate-resistant in the bone-niche.
PG  - 275
LID - 10.1186/s12967-014-0275-1 [doi]
LID - 275
AB  - INTRODUCTION: Prostate cancer bone metastasis occurs in 50-90% of men with 
      advanced disease for which there is no cure. Bone metastasis leads to 
      debilitating fractures and severe bone pain. It is associated with therapy 
      resistance and rapid decline. Androgen deprivation therapy (ADT) is standard of 
      care for advanced prostate cancer, however, bone metastatic prostate cancer (PCa) 
      often becomes resistant to ADT. There are few pre-clinical models to understand 
      the interaction between the bone microenvironment and prostate cancer. Here we 
      report the castrate resistant growth in the bone niche of PCSD1, a 
      patient-derived intra-femoral xenograft model of prostate bone metastatic cancer 
      treated with the anti-androgen, bicalutamide. METHODS: PCSD1 bone-niche model was 
      derived from a human prostate cancer femoral metastasis resected during 
      hemiarthroplasty and serially transplanted into Rag2(-/-); gamma c(-/-) mice 
      intra-femorally (IF) or sub-cutaneously (SC). At 5 weeks post-transplantation 
      mice received bicalutamide or vehicle control for 18 days. Tumor growth of PCSD1 
      was measured with calipers. PSA expression in PCSD1 xenograft tumors was 
      determined using quantitative RT-PCR and immunohistochemistry. Expression of AR 
      and PSMA, were also determined with qPCR. RESULTS: PCSD1 xenograft tumor growth 
      capacity was 24 fold greater in the bone (intra-femoral, IF) than in the soft 
      tissue (sub-cutaneous, SC) microenvironment. Treatment with the anti-androgen, 
      bicalutamide, inhibited tumor growth in the sub-cutaneous transplantation site. 
      However, bicalutamide was ineffective in suppressing PCSD1 tumor growth in the 
      bone-niche. Nevertheless, bicalutamide treatment of intra-femoral tumors 
      significantly reduced PSA expression (p < = 0.008) and increased AR (p < = 0.032) 
      relative to control. CONCLUSIONS: PCSD1 tumors were castrate resistant when 
      growing in the bone-niche compared to soft tissue. Bicalutamide had little effect 
      on reducing tumor burden in the bone yet still decreased tumor PSA expression and 
      increased AR expression, thus, this model closely recapitulated 
      castrate-resistant, human prostate cancer bone metastatic disease. PCSD1 is a new 
      primary prostate cancer bone metastasis-derived xenograft model to study bone 
      metastatic disease and for pre-clinical drug development of novel therapies for 
      inhibiting therapy resistant prostate cancer growth in the bone-niche.
FAU - Godebu, Elana
AU  - Godebu E
FAU - Muldong, Michelle
AU  - Muldong M
FAU - Strasner, Amy
AU  - Strasner A
FAU - Wu, Christina N
AU  - Wu CN
FAU - Park, Seung Chol
AU  - Park SC
FAU - Woo, Jason R
AU  - Woo JR
FAU - Ma, Wenxue
AU  - Ma W
FAU - Liss, Michael A
AU  - Liss MA
FAU - Hirata, Takeshi
AU  - Hirata T
FAU - Raheem, Omer
AU  - Raheem O
FAU - Cacalano, Nicholas A
AU  - Cacalano NA
FAU - Kulidjian, Anna A
AU  - Kulidjian AA
FAU - Jamieson, Christina A M
AU  - Jamieson CA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141003
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Androgen Antagonists)
RN  - 0 (Anilides)
RN  - 0 (Nitriles)
RN  - 0 (Tosyl Compounds)
RN  - A0Z3NAU9DP (bicalutamide)
SB  - IM
MH  - Androgen Antagonists/therapeutic use
MH  - Anilides/therapeutic use
MH  - Animals
MH  - Bone Neoplasms/drug therapy/pathology/*secondary
MH  - *Disease Models, Animal
MH  - Heterografts
MH  - Humans
MH  - Male
MH  - Mice
MH  - Nitriles/therapeutic use
MH  - *Orchiectomy
MH  - Prostatic Neoplasms/drug therapy/*pathology
MH  - Tosyl Compounds/therapeutic use
PMC - PMC4192441
EDAT- 2014/10/04 06:00
MHDA- 2016/04/14 06:00
PMCR- 2014/10/03
CRDT- 2014/10/04 06:00
PHST- 2014/08/13 00:00 [received]
PHST- 2014/09/22 00:00 [accepted]
PHST- 2014/10/04 06:00 [entrez]
PHST- 2014/10/04 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
PHST- 2014/10/03 00:00 [pmc-release]
AID - s12967-014-0275-1 [pii]
AID - 275 [pii]
AID - 10.1186/s12967-014-0275-1 [doi]
PST - epublish
SO  - J Transl Med. 2014 Oct 3;12:275. doi: 10.1186/s12967-014-0275-1.