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Active MMP-2 (active + mmp-2)

Distribution by Scientific Domains

Medical Sciences	83%

Selected Abstracts

Active MMP-2 effectively identifies the presence of colorectal cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009
Mary Jo Murnane
Abstract Fully active MMP-2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. Our study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP-2 is an effective indicator of colorectal cancer compared to pro-MMP-2 or pro-MMP-9. MMP-2 and MMP-9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer-assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP-2, pro-MMP-2 and pro-MMP-9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP-2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10-fold) than in normal mucosa. Levels of pro-MMP-2 and pro-MMP-9, but not active MMP-9, activities were also significantly higher in cancers versus normal. However, active MMP-2 activity provided the most effective test for the presence of cancer (p < 0.0.0001) with an effect size statistically significantly larger than for either pro-MMP-2 or pro-MMP-9. Receiver operating characteristic (ROC) curves demonstrated that a cut-off for active MMP-2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%. © 2009 UICC [source]

Peptide-doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor

DRUG DEVELOPMENT RESEARCH, Issue 5 2006
Gee Young Lee
Abstract Specific peptide-doxorubicin conjugates were developed for targeting matrix metalloproteinases (MMPs) expressed from tumors. The peptide-doxorubicin conjugates were designed to be cleaved by MMP-2 and MMP-9 in order that doxorubicin or the active form that acts as an anticancer agent was released free from the peptide fragment at the tumor site. Three types of peptide-doxorubicin conjugates were synthesized using the peptides: GPLG (Gly-Pro-Leu-Gly), GPLGV (Gly-Pro-Leu-Gly-Val), and GPLGPAG (Gly-Pro-Leu-Gly-Pro-Ala-Gly). The synthesized peptide-doxorubicin conjugates were characterized for their degradation behavior and bioactivity in vitro, and their antitumoral activity was assessed using the Lewis lung carcinoma (LLC) model, which expresses MMP-2 and MMP-9. After incubation with active MMP-2 for 24,h, GPLG-doxorubicin was barely degraded, whereas GPLGV-doxorubicin and GPLGPAG-doxorubicin were considerably degraded by active MMP-2. Consequently, all peptide-doxorubicin conjugates had significantly low cytotoxicity compared to doxorubicin, but tumor growth suppression was exhibited only by GPLGV-doxorubicin and GPLGPAG-doxorubicin. The tumor growth suppression by the two conjugates was higher compared to control, although it did not exceed the suppression level shown by doxorubicin. The low toxicity exhibited by peptide-doxorubicin conjugates resulted in only slight body weight loss in mice, whereas doxorubicin greatly reduced body weight and induced severe side effects. Therefore, we propose MMPs-specific peptide-doxorubicin conjugates in targeting anti-cancer drug delivery that could reduce systemic toxicities. Drug Dev. Res. 67:438,447, 2006. © 2006 Wiley-Liss, Inc. [source]

Active MMP-2 effectively identifies the presence of colorectal cancer

IFN-, withdrawal after immunotherapy potentiates B16 melanoma invasion and metastasis by intensifying tumor integrin ,v,3 signaling

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008
Wei Gong
Abstract Immunotherapy can effectively suppress tumor, yet complete tumor eradication occurs infrequently. The metastatic potential of remnant tumor cells after immunotherapy and the underlying mechanisms have not been fully elucidated. Here, we report that the termination of immunotherapy strikingly increases the metastatic potential of remnant melanoma. This is mainly due to the withdrawal of IFN-, after immunotherapy. The relief of IFN-, stress led to the increase of ,v,3 integrin expression in B16 cells, which increased the adhesion of B16 cells to fibrinogen, fibronectin and laminin. Through ,v,3 signaling, the activation of FAK, upregulation of cdc2, production of active MMP-2 and MMP-9 and actin polymerization were intensified in B16 cells stimulated with ECM molecules 24 h after the withdrawal of IFN-,. The i.v. injection of such tumor cells into mice resulted in more metastatic tumor nodes in lung and shortened the survival of mice. The pitfall of immunotherapy termination can be remedied by the administration of recombinant CBD-HepII polypeptide of fibronectin, which effectively inhibits ,v,3 signaling. These findings suggest that the risk of tumor metastasis can be increased after the termination of immunotherapy, due to the withdrawal of IFN-, and that targeting ,v,3 signaling pathway can improve the therapeutic effect of immunotherapeutic approaches by reducing such metastatic risk. © 2008 Wiley-Liss, Inc. [source]

Calcaneal Tendon Regions Exhibit Different MMP-2 Activation After Vertical Jumping and Treadmill Running

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 10 2009
Olga Cristina De Mello Malheiro
Abstract Increased activity of matrix metalloproteinases (MMPs) -2 and -9 was found in calcaneal tendon after physical training. However, little attention has been given to the distinct biomechanical and tissue structure of the calcaneal tendon's proximal and distal regions. Herein, we evaluated the effect of two types of physical activities on tendon morphology and matrix metalloproteinase activities in the proximal and distal regions of rat calcaneal tendon, separately. Adult male Wistar rats from control, water-adapted, vertical-jumping, and treadmill-running groups were sacrificed after 1 or 4 days of physical exercise, 6 hr after the end of that day's exercise session. Tendons were processed for histology, morphometry, and gelatin zymography. Tendons from adapted and trained animals showed active secretory cells and increased thickness, cellularity, and blood vessel volume fraction of peritendinous sheath, but without inflammatory process. In the proximal region, both pro- and active MMP-2 were increased after vertical jumping, but only pro-MMP-2 was increased after treadmill running. In contrast, in the distal region, both exercise types increased the activity of pro- and active MMP-2, especially treadmill running, which increased the active MMP-2 by about 11- and eightfold, respectively, after 1 and 4 days of training. No activity of MMP-9 was observed in either tendon region in this study. In conclusion, distal and proximal regions of calcaneal tendon exhibit differential intensities of tissue remodeling after treadmill running or vertical jumping and MMP-2, in the absence of inflammation, plays a major role in this adaptive response. Anat Rec, 2009. © 2009 Wiley-Liss, Inc. [source]

Low molecular weight inhibitors of matrix metalloproteinases can enhance the expression of matrix metalloproteinase-2 (gelatinase A) without inhibiting its activation

CANCER, Issue 6 2003
Erika H. M. Kerkvliet Ph.D.
Abstract BACKGROUND In the current study, the authors investigated the effects of synthetic low molecular weight inhibitors of matrix metalloproteinases (MMPs) on the expression and activation of MMP-2 in a three-dimensional tissue system. METHODS Rabbit periosteal explants were cultured with or without various concentrations of the MMP inhibitors CT1166, CT1399, or CT1746, and conditioned media and tissue extracts were analyzed for the expression and activity of MMP-2. RESULTS The data showed that blocking the activity of all MMPs with relatively high inhibitor concentrations completely prevented the conversion of pro-MMP-2 into its active form and that the level of protein was decreased. Selective inhibition of the activity of gelatinases (MMP-2 and MMP-9) by using low inhibitor concentrations, however, induced a higher level of active MMP-2 and increased its expression significantly. CONCLUSIONS The current observations indicate that selective inhibitors of MMPs affect the expression and activity of MMP-2, thus providing clues regarding the differing effects such inhibitors appear to have when applied in vivo. Cancer 2003;97:1582,88. © 2003 American Cancer Society. DOI 10.1002/cncr.11193 [source]