PMID- 14744783
OWN - NLM
STAT- MEDLINE
DCOM- 20040402
LR  - 20191108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 2
DP  - 2004 Jan 15
TI  - Matrix metalloproteinase-7 facilitates insulin-like growth factor bioavailability 
      through its proteinase activity on insulin-like growth factor binding protein 3.
PG  - 665-71
AB  - Matrix metalloproteinase-7 (MMP-7) secreted by cancer cells has been implicated 
      classically in the basement membrane destruction associated with tumor cell 
      invasion and metastasis. Recent epidemiologic studies have established a 
      correlation between high levels of circulating insulin-like growth factor (IGF) 
      and low levels of IGF binding protein 3 (IGFBP-3), and relative risk of 
      developing colon, breast, prostate, and lung cancer, which are known to produce 
      MMP-7. In this study, IGFBP-3 was assessed as a candidate for the physiologic 
      substrate of MMP-7. MMP-7 proteolysis generated four major fragments (26 kDa, 17 
      kDa, 15.5 kDa, and 15.5 kDa), and two cleavage sites were identified: one at the 
      site of hydrolysis of the K(144)-I(145) peptide bond and one at the R(95)-L(96) 
      peptide bond. The former site is different from the previously reported site of 
      cleavage of IGFBP-3 by other proteases. Addition of IGFBP-3 inhibited 
      IGF-I-mediated IGF type 1 receptor (IGF-IR) phosphorylation and activation of the 
      downstream molecule Akt in BALB/c 3T3 fibroblasts overexpressing human IGF-IR 
      (3T3-IGF-IR) and in two human colon cancer cell lines (COLO201 and HT29). 
      Coincubation of the IGF-I/IGFBP-3 complex with MMP-7 restored IGF-I-mediated 
      IGF-IR phosphorylation and activation of Akt in these cell lines. The IGF-I 
      signal recovered by MMP-7 protected against apoptosis induced by anoikis in 
      3T3-IGF-IR cells. These results indicate that MMP-7 proteolysis of IGFBP-3 plays 
      a crucial role in regulating IGF-I bioavailability, thereby promoting cell 
      survival. This mechanism may contribute to the tumorigenesis of MMP-7-producing 
      IGF-IR-expressing tumors in the primary site and to organ-specific metastasis in 
      a paracrine manner.
FAU - Miyamoto, Shin'ichi
AU  - Miyamoto S
AD  - Pathology Division, National Cancer Center Research Institute East, Chiba, Japan.
FAU - Yano, Keiichi
AU  - Yano K
FAU - Sugimoto, Seiji
AU  - Sugimoto S
FAU - Ishii, Genichiro
AU  - Ishii G
FAU - Hasebe, Takahiro
AU  - Hasebe T
FAU - Endoh, Yasushi
AU  - Endoh Y
FAU - Kodama, Keiji
AU  - Kodama K
FAU - Goya, Masato
AU  - Goya M
FAU - Chiba, Tsutomu
AU  - Chiba T
FAU - Ochiai, Atsushi
AU  - Ochiai A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Availability
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms
MH  - Endopeptidases/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/chemistry/*metabolism
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Kinetics
MH  - Matrix Metalloproteinase 7/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Peptide Fragments/chemistry/metabolism
MH  - Phosphorylation
MH  - Recombinant Proteins/chemistry/metabolism
EDAT- 2004/01/28 05:00
MHDA- 2004/04/03 05:00
CRDT- 2004/01/28 05:00
PHST- 2004/01/28 05:00 [pubmed]
PHST- 2004/04/03 05:00 [medline]
PHST- 2004/01/28 05:00 [entrez]
AID - 10.1158/0008-5472.can-03-1916 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Jan 15;64(2):665-71. doi: 10.1158/0008-5472.can-03-1916.