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Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy

Cancer metastasis is a stage of the disease where therapy is mostly ineffective; hence, the need to find reliable markers of its onset. The metalloproteinase-9 (MMP-9, gelatinase B) in its 82 kDa active form, is a good candidate, but here we show that the correspondent little known 65 kDa active MMP...

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Autores principales: Rossano, Rocco, Larocca, Marilena, Macellaro, Margherita, Bilancia, Domenico, Riccio, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929130/
https://www.ncbi.nlm.nih.gov/pubmed/35723387
http://dx.doi.org/10.3390/cimb44010008
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author Rossano, Rocco
Larocca, Marilena
Macellaro, Margherita
Bilancia, Domenico
Riccio, Paolo
author_facet Rossano, Rocco
Larocca, Marilena
Macellaro, Margherita
Bilancia, Domenico
Riccio, Paolo
author_sort Rossano, Rocco
collection PubMed
description Cancer metastasis is a stage of the disease where therapy is mostly ineffective; hence, the need to find reliable markers of its onset. The metalloproteinase-9 (MMP-9, gelatinase B) in its 82 kDa active form, is a good candidate, but here we show that the correspondent little known 65 kDa active MMP-9 isoform, often misrepresented with the other gelatinase MMP-2, is a more suitable marker. Sera from patients with lung and breast cancer were analyzed by bidimensional zymography to detect the activity of MMP-9 and MMP-2. Enzyme identity was confirmed by comparison with MMP-9 standards and by western blotting. The 65 kDa isoform of MMP-9 is a suitable biomarker to monitor tumor progression from tissue neoplasms to metastatic stage, as its activity begins to appear when disease severity increases and becomes very high in metastasis. Moreover, the 65 kDa MMP-9, which derives from the 82 kDa MMP-9, no longer responds to natural MMP-9 inhibitors. As its activity cannot be controlled, its appearance may warn that the pathological process is becoming irreversible. Identification and inhibition of the enzymes converting the inhibitor-sensitive 82 kDa MMP-9 into the corresponding “wild” 65 kDa MMP-9 may allow to develop therapies capable of blocking metastases.
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spelling pubmed-89291302022-06-04 Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy Rossano, Rocco Larocca, Marilena Macellaro, Margherita Bilancia, Domenico Riccio, Paolo Curr Issues Mol Biol Article Cancer metastasis is a stage of the disease where therapy is mostly ineffective; hence, the need to find reliable markers of its onset. The metalloproteinase-9 (MMP-9, gelatinase B) in its 82 kDa active form, is a good candidate, but here we show that the correspondent little known 65 kDa active MMP-9 isoform, often misrepresented with the other gelatinase MMP-2, is a more suitable marker. Sera from patients with lung and breast cancer were analyzed by bidimensional zymography to detect the activity of MMP-9 and MMP-2. Enzyme identity was confirmed by comparison with MMP-9 standards and by western blotting. The 65 kDa isoform of MMP-9 is a suitable biomarker to monitor tumor progression from tissue neoplasms to metastatic stage, as its activity begins to appear when disease severity increases and becomes very high in metastasis. Moreover, the 65 kDa MMP-9, which derives from the 82 kDa MMP-9, no longer responds to natural MMP-9 inhibitors. As its activity cannot be controlled, its appearance may warn that the pathological process is becoming irreversible. Identification and inhibition of the enzymes converting the inhibitor-sensitive 82 kDa MMP-9 into the corresponding “wild” 65 kDa MMP-9 may allow to develop therapies capable of blocking metastases. MDPI 2021-12-25 /pmc/articles/PMC8929130/ /pubmed/35723387 http://dx.doi.org/10.3390/cimb44010008 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rossano, Rocco
Larocca, Marilena
Macellaro, Margherita
Bilancia, Domenico
Riccio, Paolo
Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
title Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
title_full Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
title_fullStr Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
title_full_unstemmed Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
title_short Unveiling a Hidden Biomarker of Inflammation and Tumor Progression: The 65 kDa Isoform of MMP-9 New Horizons for Therapy
title_sort unveiling a hidden biomarker of inflammation and tumor progression: the 65 kda isoform of mmp-9 new horizons for therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929130/
https://www.ncbi.nlm.nih.gov/pubmed/35723387
http://dx.doi.org/10.3390/cimb44010008
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