Design and characterization of a metalloproteinase inhibitor-tethered resin for the detection of active MMPs in biological samples

Chemistry & Biology
Dusan HesekShahriar Mobashery

Abstract

Matrix metalloproteinases (MMPs), zinc-dependent endopeptidases, are implicated in tumor progression. We describe herein the development of a resin-immobilized, broad-spectrum synthetic MMP inhibitor for selective binding of the active forms of MMPs from different experimental samples. We confirmed the activity-based binding of MMPs to the inhibitor-tethered resin with purified human recombinant MMP-2, -9, and -14, samples of cultured cells, and tissue extracts. Our results show that only the free active MMPs, and not the zymogens or MMP/TIMP (enzyme-protein inhibitor) complexes, bound specifically to the resin. In our comparison of benign and carcinoma tissue extracts, we detected active MMP-2 and MMP-14 forms only in the cancerous tissue samples, indicating that a pool of the tumor MMPs is free of endogenous inhibitors (TIMPs), and is thus likely to contribute to proteolytic events that precipitate tumor metastasis.

References

Sep 9, 1986·Biochemistry·W M Moore, C A Spilburg
Mar 1, 1993·Clinical & Experimental Metastasis·P D BrownA Howell
Apr 6, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·G MurphyJ Gavrilovic
Apr 6, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·P D Brown
May 4, 1999·The Journal of Clinical Investigation·W G Stetler-Stevenson
Jun 5, 1999·Cancer Chemotherapy and Pharmacology·W P Steward
Jul 23, 1999·Annals of the New York Academy of Sciences·G MurphyC López-Otín
Mar 10, 2000·Biochimica Et Biophysica Acta·K BrewH Nagase
Mar 31, 2000·Molecular Medicine Today·L J McCawley, L M Matrisian
Feb 7, 2001·Journal of the National Cancer Institute·M Hidalgo, S G Eckhardt
Apr 27, 2001·Seminars in Cancer Biology·W G Stetler-Stevenson, A E Yu
Jul 18, 2001·Journal of the American Chemical Society·L P KotraS Mobashery
Jan 5, 2002·Journal of the National Cancer Institute·Jeffrey A NemethMichael L Cher
Mar 30, 2002·Science·Lisa M CoussensLynn M Matrisian
May 7, 2002·Nature Reviews. Cancer·Mikala Egeblad, Zena Werb
Feb 27, 2003·Breast Cancer Research and Treatment·Lydia NakopoulouPanayiotis S Davaris
Jun 6, 2003·The Journal of Surgical Research·John E BartschHubert E Appert
Aug 7, 2003·Biochemical and Biophysical Research Communications·Marta TothRafael Fridman
Jan 20, 2004·Trends in Cell Biology·Amos BaruchMatthew Bogyo
Mar 24, 2004·Current Opinion in Chemical Biology·Nadim Jessani, Benjamin F Cravatt
Jun 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alan SaghatelianBenjamin F Cravatt
Sep 7, 2004·The International Journal of Developmental Biology·Alicia R FolguerasCarlos López-Otín
Sep 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nadim JessaniBenjamin F Cravatt
Nov 17, 2004·The Journal of Cell Biology·Tae-Hwa ChunStephen J Weiss
May 4, 2005·Cancer Research·Achim KrügerRafael Fridman
Sep 9, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Barbara Fingleton

❮ Previous
Next ❯

Citations

Dec 29, 2012·The Journal of Biological Chemistry·Catherine NuryVincent Dive
Aug 13, 2011·BMC Cancer·Pia BoströmPirkko Hirsimäki
Dec 19, 2006·Current Opinion in Chemical Biology·Amir M SadaghianiMatthew Bogyo
Nov 15, 2011·British Journal of Pharmacology·Chris W Sutton
Apr 4, 2013·Critical Reviews in Biochemistry and Molecular Biology·Jennifer VandoorenGhislain Opdenakker
Dec 4, 2012·Chembiochem : a European Journal of Chemical Biology·Catherine NuryVincent Dive
Jan 27, 2011·Journal of Biomedical Materials Research. Part a·Yang CaoTim R Dargaville
Apr 25, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Jayda E Meisel, Mayland Chang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.