PMID- 19608765
OWN - NLM
STAT- MEDLINE
DCOM- 20090828
LR  - 20211020
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 23
IP  - 16
DP  - 2009 Aug 15
TI  - ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic 
      signaling cascade for bone metastasis.
PG  - 1882-94
LID - 10.1101/gad.1824809 [doi]
AB  - Bone metastasis is mediated by complex interactions between tumor cells and 
      resident stromal cells in the bone microenvironment. The functions of 
      metalloproteinases in organ-specific metastasis remain poorly defined despite 
      their well-appreciated role in matrix degradation and tumor invasion. Here, we 
      show a mechanism whereby two distinct metalloproteinases, a disintegrin and 
      metalloproteinase with thrombospondin motifs (ADAMTS1) and matrix 
      metalloproteinase-1 (MMP1), orchestrate a paracrine signaling cascade to modulate 
      the bone microenvironment in favor of osteoclastogenesis and bone metastasis. 
      Proteolytic release of membrane-bound epidermal growth factor (EGF)-like growth 
      factors, including Amphiregulin (AREG), heparin-binding EGF (HB-EGF), and 
      transforming growth factor alpha (TGFalpha) from tumor cells suppress the 
      expression of osteoprotegerin (OPG) in osteoblasts and subsequently potentiate 
      osteoclast differentiation. EGF receptor (EGFR) inhibitors block osteolytic bone 
      metastasis by targeting EGFR signaling in bone stromal cells. Furthermore, 
      elevated MMP1 and ADAMTS1 expression is associated with increased risk of bone 
      metastasis in breast cancer patients. This study established MMP1 and ADAMTS1 in 
      tumor cells, as well as EGFR signaling in osteoblasts, as promising therapeutic 
      targets for inhibiting bone metastasis of breast cancer.
FAU - Lu, Xin
AU  - Lu X
AD  - Department of Molecular Biology, Princeton University, Princeton, New Jersey 
      08544, USA.
FAU - Wang, Qiongqing
AU  - Wang Q
FAU - Hu, Guohong
AU  - Hu G
FAU - Van Poznak, Catherine
AU  - Van Poznak C
FAU - Fleisher, Martin
AU  - Fleisher M
FAU - Reiss, Michael
AU  - Reiss M
FAU - Massague, Joan
AU  - Massague J
FAU - Kang, Yibin
AU  - Kang Y
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090716
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Osteoprotegerin)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 0 (RANK Ligand)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAMTS1 Protein)
RN  - EC 3.4.24.- (ADAMTS1 protein, human)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - S65743JHBS (Gefitinib)
SB  - IM
CIN - Immunotherapy. 2009 Nov;1(6):925-7
CIN - Genes Dev. 2009 Sep 15;23(18):2117-23. PMID: 19759260
MH  - ADAM Proteins/genetics/*metabolism
MH  - ADAMTS1 Protein
MH  - Animals
MH  - Bone Neoplasms/enzymology/genetics/*secondary
MH  - Bone and Bones/cytology/pathology
MH  - Breast Neoplasms/enzymology/genetics/*pathology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Epidermal Growth Factor/*metabolism
MH  - Female
MH  - Gefitinib
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Silencing
MH  - Matrix Metalloproteinase 1/genetics/*metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Osteoblasts/cytology/metabolism
MH  - Osteoprotegerin/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Quinazolines/pharmacology
MH  - RANK Ligand/metabolism
MH  - *Signal Transduction
PMC - PMC2725946
EDAT- 2009/07/18 09:00
MHDA- 2009/08/29 09:00
PMCR- 2010/02/15
CRDT- 2009/07/18 09:00
PHST- 2009/07/18 09:00 [entrez]
PHST- 2009/07/18 09:00 [pubmed]
PHST- 2009/08/29 09:00 [medline]
PHST- 2010/02/15 00:00 [pmc-release]
AID - gad.1824809 [pii]
AID - 10.1101/gad.1824809 [doi]
PST - ppublish
SO  - Genes Dev. 2009 Aug 15;23(16):1882-94. doi: 10.1101/gad.1824809. Epub 2009 Jul 
      16.