PMID- 29632317
OWN - NLM
STAT- MEDLINE
DCOM- 20191004
LR  - 20230816
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Apr 9
TI  - Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In 
      Mammary Tumorigenesis.
PG  - 5717
LID - 10.1038/s41598-018-24022-w [doi]
LID - 5717
AB  - Plac1 is an X-linked trophoblast gene expressed at high levels in the placenta, 
      but not in adult somatic tissues other than the testis. Plac1 however is 
      re-expressed in several solid tumors and in most human cancer cell lines. To 
      explore the role of Plac1 in cancer progression, Plac1 was reduced by RNA 
      interference in EO771 mammary carcinoma cells. EO771 "knockdown" (KD) resulted in 
      50% reduction in proliferation in vitro and impaired tumor growth in syngeneic 
      mice; however, tumor growth in SCID mice was equivalent to tumor cells expressing 
      a non-silencing control RNA, suggesting that Plac1 regulated adaptive immunity. 
      Gene expression profiling of Plac1 KD cells indicated reduction in several 
      inflammatory and immune factors, including Cxcl1, Ccl5, Ly6a/Sca-1, Ly6c and Lif. 
      Treatment of mice engrafted with wild-type EO771 cells with a Cxcr2 antagonist 
      impaired tumor growth, reduced myeloid-derived suppressor cells and regulatory T 
      cells, while increasing macrophages, dendritic cells, NK cells and the 
      penetration of CD8+ T cells into the tumor bed. Cxcl1 KD phenocopied the effects 
      of Plac1 KD on tumor growth, and overexpression of Cxcl1 partially rescued Plac1 
      KD cells. These results reveal that Plac1 modulates a tolerogenic tumor 
      microenvironment in part by modulating the chemokine axis.
FAU - Yuan, Hongyan
AU  - Yuan H
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Wang, Xiaoyi
AU  - Wang X
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Shi, Chunmei
AU  - Shi C
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Jin, Lu
AU  - Jin L
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Hu, Jianxia
AU  - Hu J
AD  - Laboratory of Thyroid Diseases, the Affiliated Hospital of Qingdao University, 
      Qingdao, 266003, China.
FAU - Zhang, Alston
AU  - Zhang A
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Li, James
AU  - Li J
AD  - Department of Bioinformatics, Biostatistics and Biomathematics, Georgetown 
      University Medical Center, Washington, DC, 20007, USA.
FAU - Vijayendra, Nairuthya
AU  - Vijayendra N
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Doodala, Venkata
AU  - Doodala V
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Weiss, Spencer
AU  - Weiss S
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Tang, Yong
AU  - Tang Y
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Weiner, Louis M
AU  - Weiner LM
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA.
FAU - Glazer, Robert I
AU  - Glazer RI
AD  - Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown 
      University, Washington, DC, 20007, USA. glazerr@georgetown.edu.
LA  - eng
GR  - N01CN43302/CA/NCI NIH HHS/United States
GR  - P30 CA051008/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180409
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Chemokines)
RN  - 0 (PLAC1 protein, mouse)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Interleukin-8B)
SB  - IM
MH  - Adaptive Immunity
MH  - Animals
MH  - Breast Neoplasms/genetics/*immunology/*pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Chemokines/*genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - Pregnancy Proteins/*genetics/metabolism
MH  - RNA, Small Interfering/*pharmacology
MH  - Receptors, Interleukin-8B/antagonists & inhibitors
MH  - Transplantation, Isogeneic
MH  - Tumor Microenvironment
PMC - PMC5890253
COIS- The authors declare no competing interests.
EDAT- 2018/04/11 06:00
MHDA- 2019/10/08 06:00
PMCR- 2018/04/09
CRDT- 2018/04/11 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2018/03/22 00:00 [accepted]
PHST- 2018/04/11 06:00 [entrez]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2018/04/09 00:00 [pmc-release]
AID - 10.1038/s41598-018-24022-w [pii]
AID - 24022 [pii]
AID - 10.1038/s41598-018-24022-w [doi]
PST - epublish
SO  - Sci Rep. 2018 Apr 9;8(1):5717. doi: 10.1038/s41598-018-24022-w.