ArticleLeukemia2005
Targeting an MMP-9-activated prodrug to multiple myeloma-diseased bone marrow: a proof of principle in the 5T33MM mouse model.
Article in Leukemia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 32 citations in OpenAlex.
- Recent Advances in the Enzyme-Activatable Organic Fluorescent Probes for Tumor Imaging and Therapy.ChemistryOpen · 2022Review
- Plasma Cell Leukemia - Facts and Controversies: More Questions than Answers?Clinical hematology international · 2020Review
- Principles in the design of ligand-targeted cancer therapeutics and imaging agents.Nature reviews. Drug discovery · 2015Review
- Article
- Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia.ACS nano · 2011Article
- Tumour endoproteases: the cutting edge of cancer drug delivery?British journal of pharmacology · 2008Review
- Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise.Current pharmaceutical design · 2008Review
- Matrix metalloproteases: underutilized targets for drug delivery.Journal of drug targeting · 2007Review
- Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma.Oncogene · 2006Review
- A murine model of myeloma that allows genetic manipulation of the host microenvironment.Disease models & mechanismsArticle
- Moving targets: Emerging roles for MMPs in cancer progression and metastasis.Matrix biology : journal of the International Society for Matrix BiologyReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is an incurable B-cell cancer characterised by the monoclonal proliferation of tumour cells in the bone marrow (BM). It has been described that matrix metalloproteinases (MMPs) and especially MMP-9 is secreted by MM cells. In this study, we investigated the possibility to exploit MMP-9 activity to activate prodrugs and to target MM cells as a new tumour-specific therapy. Cleavage of the prodrug EV1-FITC by MMP-9 resulted in release of fluorescence which can be used as a measure of prodrug activation. The 5T33MM mouse model was used in this proof-of-principle study. The prodrug was activated in a higher amount by addition to MMP-9-producing 5T33MMvv cells, homogenates from tumour-bearing organs (BM, spleen) and isolated 5T33MM-diseased BM and spleen cells compared to non-MMP-9-producing 5T33MMvt cells and homogenates/cells from non-tumour-bearing organs/mice, as measured by fluorescence release. This fluorescence release could be inhibited by the MMP-2/MMP-9-specific inhibitor, CTT. Activation of the prodrug in the 5T33MM spleen and BM homogenates was confirmed by chromatography. EV1-fluorescein isothiocyanate injection into 5T33MM-diseased animals resulted in a higher fluorescence release by the isolated BM and spleen cells compared to injection into healthy animals. In conclusion, MMP-9 activity can be used to activate prodrugs that target MM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.