A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies

A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies

Author Pereira, Felipe Valença Autor UNIFESP Google Scholar
Ferreira-Guimaraes, Carla A. Autor UNIFESP Google Scholar
Paschoalin, Thaysa Autor UNIFESP Google Scholar
Scutti, Jorge Augusto Borin Autor UNIFESP Google Scholar
Melo, Filipe Menegatti de Autor UNIFESP Google Scholar
Silva, Luis S. Autor UNIFESP Google Scholar
Melo, Amanda C. L. Autor UNIFESP Google Scholar
Silva, Priscila Autor UNIFESP Google Scholar
Tiago, Manoela Google Scholar
Matsuo, Alisson Leonardo Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Rodrigues, Elaine Guadelupe Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 10/51423-0
FAPESP: 12/50191-4
Date 2014-04-30
Published in Plos One. San Francisco: Public Library Science, v. 9, n. 4, 11 p., 2014.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 11
Origin http://dx.doi.org/10.1371/journal.pone.0096141
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000338917300028
URI http://repositorio.unifesp.br/handle/11600/37679

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