Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability

Nakamura, Michio; Miyamoto, Shin’ichi; Maeda, Hitoshi; Ishii, Genichiro; Hasebe, Takahiro; Chiba, Tsutomu; Asaka, Masahiro; Ochiai, Atsushi

doi:10.1016/j.bbrc.2005.06.010

Cited by 107 publications

(83 citation statements)

References 45 publications

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“…Matrisian et al (35) showed that intestinal polyp formation in Apc Min/+ mice is prevented by the absence of matrix metalloproteinase-7 (MMP-7) and by the administration of the MMP inhibitor, batimastat (36). We showed previously that MMP-7 acts as a pan-IGFBP protease (37). Because MMP-7 acts as a tissue protease, these data suggest that MMP-7 accelerates polyp formation by increasing the concentration of free/bioactive IGFs through its IGFBP protease activity in the tissue microenvironment.…”

Section: Discussionmentioning

confidence: 73%

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Matsunaka

Miyamoto

Shitara

et al. 2010

Molecular Cancer Therapeutics

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Insulin-like growth factors (IGF-I and IGF-II) play important roles in intestinal tumorigenesis. To investigate the effectiveness of IGF-targeting strategies, we conducted an in vivo study using anti-mouse neutralizing antibodies IGF-I (KM3168) and IGF-II (KM1468). Six-and 10-week-old Apc +/− mice were given KM3168 and/or KM1468 i.p. at two doses (0.01 or 0.1 μg/g weight) once or twice weekly for 4 weeks. To clarify the source of IGFs in vivo, we evaluated the expression levels of IGFs in the liver, normal small intestine, and polyps of the small intestine of Apc +/− mice. The phosphorylation status of IGF signalrelated molecules was examined using immunostaining to understand the mechanism underlying the effects of IGF-neutralizing antibody. The plasma half-life was 168 for KM3168 and 85 hours for KM1468. In two lineages of Apc +/− mice (Apc 1309 and Apc Min/+ ), a low dose (0.01 μg/g weight) of KM3168 and KM1468 significantly reduced the number of polyps when given once and twice weekly, respectively. Combined administration of the effective dose of each antibody had an additive effect. The liver was the main source of IGF-I, whereas the polyps of the small intestine and normal small intestine were the main source of IGF-II. IGF-neutralizing antibodies decreased the phosphorylation of IGF type 1 receptor and inhibited the signal transduction of the Akt pathway. These results suggest that IGF-I and IGF-II play important roles in polyp formation in Apc +/− mice and that specific antibodies to IGF-I and IGF-II may be promising antitumor agents. Mol Cancer Ther; 9(2); 419-28. ©2010 AACR.

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Section: Discussionmentioning

confidence: 73%

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Matsunaka

Miyamoto

Shitara

et al. 2010

Molecular Cancer Therapeutics

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“…Recent data have shown that MMP-7 possesses pan-IGFBP protease activity (Nakamura et al 2005). MMP-7 proteolysis of IGFBP-3 plays a crucial role in regulating IGF-I bioavailability and thus promotes cell survival (Miyamoto et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Serum IGF-I, IGFBP-3, and matrix metalloproteinase-7 levels and acquired chemo-resistance in advanced colorectal cancer

Gallego¹,

Codony-Servat²,

García-Albéniz³

et al. 2009

Endocrine-Related Cancer

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Insulin-like growth factor-I (IGF-I) is thought to have antiapoptotic and mitogenic properties in colorectal cancer, whereas IGF-binding protein-3 (IGFBP-3) seems to exert a pro-apoptotic effect. Additionally, matrix metalloproteinase-7 (MMP-7), an enzyme with in vitro ability to degrade IGFBP-3, has been shown to be a prognostic factor in advanced colorectal cancer (ACRC). We studied whether chemotherapy treatment for ACRC modulates IGF-I, IGFBP-3, and MMP-7 serum levels. In 41 patients undergoing first-line therapy for ACRC, serum levels of IGF-I, IGFBP-3, and MMP-7 were measured with immunoassays at baseline and every 3 months until progressive disease, or a maximum of five determinations, during a chemotherapy regimen of either FOLFOX or FOLFIRI therapies. Associations were assessed for paired samples, using t-test or Wilcoxon ranks test depending on normality of the variable, verified with Shapiro-Wilk test. An average of four extractions (range 3-5) were done, for a total of 157 determinations. Mean pretreatment values of IGF-I, IGFBP-3, and MMP-7 were 83 (95% CI, 73-92) ng/ml, 2372 (95% CI, 2121-2623) ng/ml, and 10.6 (95% CI, 7.21-13.98) ng/ml respectively. No significant changes in IGF-I were found, but a significant increase in IGFBP-3 serum concentrations was observed during or after chemotherapy treatment without progressive disease, compared with basal levels (P!0.001). A significant decrease in IGFBP-3 to 1983 ng/ml (95% CI, 1675-2292) and a significant increase in MMP-7 levels to 14.6 (7.6-21.7) ng/ml were observed at progression of disease compared with baseline and treatment levels (P!0.001). This study shows that IGFBP-3 and MMP-7 serum levels change during chemotherapy treatment. The increased MMP-7 levels at disease progression support the hypothesis that this protease could play a role in acquired resistance by degrading IGFBP-3.

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“…IGFBPPs are present both in circulation and in interstitial fluids, and their activity is kept in check by endogenous protease activators and inhibitors Bunn and Fowlkes, 2003;Holly, 2004). Among the IGFBPPs reported are serine proteinases (complement protein 1s; kallikreins such as prostate-specific antigen, human kallikrein 2 and 7S nerve growth factor; plasmin; a HtrA-related protease; seminal plasma trypsin; cathepsin G and neutrophil elastase; and thrombin), cysteine proteinases (cathepsins and calpain), and metalloproteases (MPs) from the adamalysin/ADAM (ADAM-9, -12 and -28) and matrix metalloprotease (MMP) families (Fowlkes et al, 1994;Maile and Holly, 1999;Bunn and Fowlkes, 2003;Fang et al, 2004;Burger et al, 2005;Nakamura et al, 2005). The latter two families are involved in the regulation of other growth factor families through the shedding of ectodomains of membrane-anchored growth factors, cytokines and receptors to increase their circulating forms (Gomis-Rü th et al, 1998;Overall and Ló pez-Otín, 2002;Arribas and Merlos-Suá rez, 2003;Blobel, 2005).…”

Section: Introductionmentioning

confidence: 99%

Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

Tallant

García‐Castellanos

Marrero

et al. 2007

BCHM

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Human growth and development are conditioned by insulin-like growth factors (IGFs), which have also implications in pathology. Most IGF molecules are sequestered by IGF-binding proteins (IGFBPs) so that exertion of IGF activity requires disturbance of these complexes. This is achieved by proteolysis mediated by IGFBP proteases, among which the best characterised is human PAPP-A, the first member of the pappalysin family of metzincins. We have previously identified and studied the only archaeal homologue found to date, Methanosarcina acetivorans ulilysin. This is a proteolytically functional enzyme encompassing a pappalysin catalytic domain and a pro-domain involved in maintenance of latency of the zymogen, proulilysin. Once activated, the protein hydrolyses IGFBP-2 to -6 and insulin chain b in vitro. We report here that ulilysin is also active against several other substrates, viz (azo)casein, azoalbumin, and extracellular matrix components. Ulilysin has gelatinolytic but not collagenolytic activity. Moreover, the proteolysis-resistant skeletal proteins actin and elastin are also cleaved, as is fibrinogen, but not plasmin and a1-antitrypsin from the blood coagulation cascade. Ulilysin develops optimal activity at pH 7.5 and strictly requires peptide bonds preceding an arginine residue, as determined by means of a novel fluorescence resonance energy transfer assay, thus pointing to biotechnological applications as an enzyme complementary to trypsin.These two authors contributed equally to this work. a

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Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability

Cited by 107 publications

References 45 publications

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Serum IGF-I, IGFBP-3, and matrix metalloproteinase-7 levels and acquired chemo-resistance in advanced colorectal cancer

Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

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