PMID- 26025665
OWN - NLM
STAT- MEDLINE
DCOM- 20160218
LR  - 20181113
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 17
IP  - 5
DP  - 2015 May
TI  - Presence of insulin-like growth factor binding proteins correlates with 
      tumor-promoting effects of matrix metalloproteinase 9 in breast cancer.
PG  - 421-33
LID - S1476-5586(15)00047-0 [pii]
LID - 10.1016/j.neo.2015.04.003 [doi]
AB  - The stroma of breast cancer can promote the disease's progression, but whether 
      its composition and functions are shared among different subtypes is poorly 
      explored. We compared stromal components of a luminal [mouse mammary tumor virus 
      (MMTV)-Neu] and a triple-negative/basal-like [C3(1)-Simian virus 40 large T 
      antigen (Tag)] genetically engineered breast cancer mouse model. The types of 
      cytokines and their expression levels were very different in the two models, as 
      was the extent of innate immune cell infiltration; however, both models showed 
      infiltration of innate immune cells that expressed matrix metalloproteinase 9 
      (MMP9), an extracellular protease linked to the progression of many types of 
      cancer. By intercrossing with Mmp9 null mice, we found that the absence of MMP9 
      delayed tumor onset in the C3(1)-Tag model but had no effect on tumor onset in 
      the MMTV-Neu model. We discovered that protein levels of insulin-like growth 
      factor binding protein-1 (IGFBP-1), an MMP9 substrate, were increased in 
      C3(1)-Tag;Mmp9(-/-) compared to C3(1)-Tag;Mmp9(+/+) tumors. In contrast, IGFBP-1 
      protein expression was low in MMTV-Neu tumors regardless of Mmp9 status. IGFBP-1 
      binds and antagonizes IGFs, preventing them from activating their receptors to 
      promote cell proliferation and survival. Tumors from C3(1)-Tag;Mmp9(-/-) mice had 
      reduced IGF-1 receptor phosphorylation, consistent with slower tumor onset. 
      Finally, gene expression analysis of human breast tumors showed that high 
      expression of IGFBP mRNA was strongly correlated with good prognosis but not when 
      MMP9 mRNA was also highly expressed. In conclusion, MMP9 has different effects on 
      breast cancer progression depending on whether IGFBPs are expressed.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Park, Jae-Hyun
AU  - Park JH
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
FAU - Rasch, Morten Gronbech
AU  - Rasch MG
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA; The Finsen 
      Laboratory, Rigshospitalet, Copenhagen N, Denmark.
FAU - Qiu, Jing
AU  - Qiu J
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
FAU - Lund, Ida Katrine
AU  - Lund IK
AD  - The Finsen Laboratory, Rigshospitalet, Copenhagen N, Denmark.
FAU - Egeblad, Mikala
AU  - Egeblad M
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA; University of 
      California, San Francisco, San Francisco, CA, USA. Electronic address: 
      egeblad@cshl.edu.
LA  - eng
GR  - R01 CA057621/CA/NCI NIH HHS/United States
GR  - R01CA057621/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Antigens, Viral, Tumor)
RN  - 0 (IGFBP1 protein, human)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 1)
RN  - EC 3.4.24.35 (MMP9 protein, human)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Antigens, Viral, Tumor
MH  - Breast Neoplasms/metabolism/*pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Insulin-Like Growth Factor Binding Protein 1/*biosynthesis
MH  - Kaplan-Meier Estimate
MH  - Mammary Neoplasms, Experimental/metabolism/pathology
MH  - Mammary Tumor Virus, Mouse
MH  - Matrix Metalloproteinase 9/*biosynthesis
MH  - Mice
MH  - Mice, Knockout
MH  - Polyomavirus Infections
MH  - Protein Array Analysis
MH  - Retroviridae Infections
MH  - Simian virus 40
MH  - Triple Negative Breast Neoplasms/metabolism/pathology
MH  - Tumor Virus Infections
PMC - PMC4468371
EDAT- 2015/05/31 06:00
MHDA- 2016/02/19 06:00
PMCR- 2015/05/27
CRDT- 2015/05/31 06:00
PHST- 2014/12/23 00:00 [received]
PHST- 2015/03/30 00:00 [revised]
PHST- 2015/04/09 00:00 [accepted]
PHST- 2015/05/31 06:00 [entrez]
PHST- 2015/05/31 06:00 [pubmed]
PHST- 2016/02/19 06:00 [medline]
PHST- 2015/05/27 00:00 [pmc-release]
AID - S1476-5586(15)00047-0 [pii]
AID - 10.1016/j.neo.2015.04.003 [doi]
PST - ppublish
SO  - Neoplasia. 2015 May;17(5):421-33. doi: 10.1016/j.neo.2015.04.003.