title: Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability.
abstract: Proteolytic modification of insulin-like growth factor binding proteins (IGFBPs) plays an important physiological role in regulating insulin-like growth factor (IGF) bioavailability. Recently, we demonstrated that matrix metalloproteinase-7 (MMP-7)/Matrilysin produced by various cancer cells catalyzes the proteolysis of IGFBP-3 in vitro and regulates IGF bioavailability, resulting in an anti-apoptotic effect against anchorage-independent culture. In the present study, we investigated whether MMP-7 contributes to proteolysis of the other five IGFBPs, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6, and whether this results in phosphorylation of the IGF type 1 receptor (IGF-1R). MMP-7 cleaved all six IGFBPs, resulting in IGF-mediated IGF-1R phosphorylation, which was inhibited by EDTA treatment. These results suggest that MMP-7 derived from cancer cells can regulate IGF bioavailability in the microenvironment surrounding the tumor, where various kinds of IGF/IGFBP complexes are found, thereby favoring cancer cell growth and survival during the processes of invasion and metastasis.
authors.affiliation: Pathology Division, National Cancer Center Research Institute East, Chiba, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maeda
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasebe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001682:Biological Availability; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D020783:Matrix Metalloproteinase 7