PMID- 25597486
OWN - NLM
STAT- MEDLINE
DCOM- 20150414
LR  - 20150219
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Linking)
VI  - 75
IP  - 5
DP  - 2015 Apr 1
TI  - Loss of MyD88 leads to more aggressive TRAMP prostate cancer and influences tumor 
      infiltrating lymphocytes.
PG  - 463-73
LID - 10.1002/pros.22932 [doi]
AB  - BACKGROUND: The influence of pattern recognition receptor (PRR) signaling in the 
      prostate tumor microenvironment remains unclear. Although there may be a role for 
      PRR agonists as adjuvants to therapy, prior evidence suggests tumor promoting as 
      well as tumor inhibiting mechanisms. The purpose of this study is to examine the 
      role of the key Toll-like receptor (TLR) signaling adaptor protein myeloid 
      differentiation primary response gene 88 (MyD88) in prostate cancer development. 
      METHODS: MyD88(-/-) mice in a C57Bl6 background were crossed with transgenic 
      adenocarcinomas of the mouse prostate (TRAMP) mice to create MyD88(-/-) 
      TRAMP(Tg+/-) animals, which were compared to MyD88(+/+) TRAMP(Tg+/-) animals and 
      their non-transgenic counterparts at 30 weeks. Prostates were examined 
      histologically, by immunohistochemistry and immunofluorescence staining, and by 
      qPCR, to characterize tumor-infiltrating immune populations as well as activation 
      of the downstream NF-kappaB pathway and androgen receptor (AR) expression. 
      Splenocytes were examined for development of distinct immune cell populations. 
      RESULTS: Absence of MyD88 led to increased prostatic intraepithelial neoplasm 
      (PIN) and areas of well-differentiated adenocarcinoma in TRAMP transgenic mice. 
      Analysis of infiltrating immune populations revealed an increase in CD11b(+) 
      Gr1(+) myeloid-derived suppressor cells (MDSCs), as evidenced by increased 
      expression of prostatic arginase-1 and iNOS as well as the cytokine IL-10, and a 
      deficiency in NK cells in prostates from MyD88(-/-) TRAMP(Tg+/-) compared to 
      MyD88(+/+) TRAMP(Tg+/-) mice, whereas a decrease in splenocytic NK cell 
      differentiation was observed in MyD88(-/-) mice. Prostate tumors revealed no 
      significant differences in NF-kappaB or AR expression in MyD88(+/+) TRAMP(Tg+/-) 
      compared to MyD88(-/-) TRAMP(Tg+/-) mice. CONCLUSIONS: During prostate cancer 
      development in the TRAMP model, MyD88 may play a role in limiting prostate 
      tumorigenesis by altering tumor-infiltrating immune populations. This suggests 
      that in the context of specific cancers, distinct PRRs and signaling pathways of 
      innate immune signaling may influence the tumor microenvironment and represent a 
      novel therapeutic strategy.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Peek, Elizabeth M
AU  - Peek EM
AD  - Molecular Biology Institute, UCLA, Los Angeles, California.
FAU - Song, Wang
AU  - Song W
FAU - Zhang, Hanwei
AU  - Zhang H
FAU - Huang, Jiaoti
AU  - Huang J
FAU - Chin, Arnold I
AU  - Chin AI
LA  - eng
PT  - Journal Article
DEP - 20150116
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Adenocarcinoma/*metabolism/pathology
MH  - Animals
MH  - Cell Transformation, Neoplastic/metabolism
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Immunohistochemistry
MH  - Lymphocytes, Tumor-Infiltrating/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloid Differentiation Factor 88/*physiology
MH  - NF-kappa B/metabolism
MH  - Prostatic Neoplasms/*metabolism/pathology
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Androgen/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - MyD88
OT  - NF-kappaB
OT  - TRAMP
OT  - Toll-like receptors
OT  - prostate cancer
OT  - tumor-infiltrating lymphocytes
EDAT- 2015/01/20 06:00
MHDA- 2015/04/15 06:00
CRDT- 2015/01/20 06:00
PHST- 2014/08/06 00:00 [received]
PHST- 2014/10/22 00:00 [accepted]
PHST- 2015/01/20 06:00 [entrez]
PHST- 2015/01/20 06:00 [pubmed]
PHST- 2015/04/15 06:00 [medline]
AID - 10.1002/pros.22932 [doi]
PST - ppublish
SO  - Prostate. 2015 Apr 1;75(5):463-73. doi: 10.1002/pros.22932. Epub 2015 Jan 16.