ArticlePloS one2014
A natural bacterial-derived product, the metalloprotease arazyme, inhibits metastatic murine melanoma by inducing MMP-8 cross-reactive antibodies.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Enzyme-mediated remodeling of the extracellular matrix and glycocalyx to enhance immunotherapy in solid tumors.Bioengineering & translational medicine · 2026Review
- HapA protease targets PAR-1/2 to modulate ERK signalling and reduce cancer cell viability.Cell death discovery · 2025Article
- The immunomodulatory and antitumor properties of the bacterial metalloprotease Oligopeptidase A are mediated by TLR4/MyD88/TRIF and MAPK signaling pathways.Frontiers in immunology · 2025Article
- Targeted therapies in HER2-positive breast cancer with receptor-redirected Arazyme-linker-Herceptin as a novel fusion protein.Breast cancer (Tokyo, Japan) · 2024Article
- Metallo-protease Peptidase M84 fromiScience · 2024Article
- A limitless Brazilian scientist: Professor Travassos and his contribution to cancer biology.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Review
- A comparative study of the arazyme-based fusion proteins with various ligands for more effective targeting cancer therapy: anResearch in pharmaceutical sciences · 2023Article
- Identification of a cytotoxic factor from a non-pigmented entomopathogenic Serratia marcescens isolate toxic towards human carcinoma cell lines.Archives of microbiology · 2023Article
- The Anti-Adhesion Effect of Nisin as a Robust Lantibiotic on the Colorectal Cancer Cells.Advanced biomedical research · 2023Article
- ARA-linker-TGFαL3: a novel chimera protein to target breast cancer cells.Medical oncology (Northwood, London, England) · 2021Article
- Combination Treatment of Arazyme and Soy Leaf Extract Attenuates Hyperglycemia and Hepatic Steatosis in High-Fat Diet-Fed C57BL/6J Mice.Life (Basel, Switzerland) · 2021Article
- Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model.International journal of molecular sciences · 2019Article
- TLR4-mediated immunomodulatory properties of the bacterial metalloprotease arazyme in preclinical tumor models.Oncoimmunology · 2016Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increased incidence, high rates of mortality and few effective means of treatment of malignant melanoma, stimulate the search for new anti-tumor agents and therapeutic targets to control this deadly metastatic disease. In the present work the antitumor effect of arazyme, a natural bacterial-derived metalloprotease secreted by Serratia proteomaculans, was investigated. Arazyme significantly reduced the number of pulmonary metastatic nodules after intravenous inoculation of B16F10 melanoma cells in syngeneic mice. In vitro, the enzyme showed a dose-dependent cytostatic effect in human and murine tumor cells, and this effect was associated to the proteolytic activity of arazyme, reducing the CD44 expression at the cell surface, and also reducing in vitro adhesion and in vitro/in vivo invasion of these cells. Arazyme treatment or immunization induced the production of protease-specific IgG that cross-reacted with melanoma MMP-8. In vitro, this antibody was cytotoxic to tumor cells, an effect increased by complement. In vivo, arazyme-specific IgG inhibited melanoma lung metastasis. We suggest that the antitumor activity of arazyme in a preclinical model may be due to a direct cytostatic activity of the protease in combination with the elicited anti-protease antibody, which cross-reacts with MMP-8 produced by tumor cells. Our results show that the bacterial metalloprotease arazyme is a promising novel antitumor chemotherapeutic agent.
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