Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/37679
Title: A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies
Authors: Pereira, Felipe Valença [UNIFESP]
Ferreira-Guimaraes, Carla A. [UNIFESP]
Paschoalin, Thaysa [UNIFESP]
Scutti, Jorge Augusto Borin [UNIFESP]
Melo, Filipe Menegatti de [UNIFESP]
Silva, Luis S. [UNIFESP]
Melo, Amanda C. L. [UNIFESP]
Silva, Priscila [UNIFESP]
Tiago, Manoela
Matsuo, Alisson Leonardo [UNIFESP]
Juliano, Luiz [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Carmona, Adriana Karaoglanovic [UNIFESP]
Travassos, Luiz Rodolpho [UNIFESP]
Rodrigues, Elaine Guadelupe [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Issue Date: 30-Apr-2014
Publisher: Public Library Science
Citation: Plos One. San Francisco: Public Library Science, v. 9, n. 4, 11 p., 2014.
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.
URI: http://repositorio.unifesp.br/handle/11600/37679
ISSN: 1932-6203
Other Identifiers: http://dx.doi.org/10.1371/journal.pone.0096141
Appears in Collections:Artigo
Artigo

Files in This Item:
File Description SizeFormat 
WOS000338917300028.pdf1.42 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.