title: An extracellular proteasome releases endostatin from human collagen XVIII.
abstract: Endostatin is a potent anti-angiogenic and anti-tumor protein capable of regressing tumors without inducing acquired resistance. Since it is a fragment of the parental molecule, collagen XVIII, its endogenous production depends on the activity of a specific proteolytic enzyme. While such an enzyme has been described in mice, a human counterpart has not been identified so far. Here, we searched for this enzyme by using a fluorescence resonance energy transfer peptide containing the cleavage site of human collagen XVIII. We found that the cleavage activity was present in various murine and human tumor cells but not in untransformed cells. It was ascribed to a large protein complex identified as an extracellular form of proteasome 20S. Since circulating proteasome 20S has recently emerged as an important marker of tumor progression, the possibility of proteasomes controlling the production of angiostatic endostatin may inspire the development of new anticancer therapies.
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Maria L V
authors.initials: ML
authors.lastname: Reiss-Pistilli
authors.affiliation: Institute of Translational Immunology and Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Madalena M S
authors.initials: MM
authors.lastname: Barroso
authors.affiliation: Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Iranaia
authors.initials: I
authors.lastname: Assunção-Miranda
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Shirley
authors.initials: S
authors.lastname: Farias
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Lery
authors.affiliation: Institute of Translational Immunology and Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. tcsampaio@histo.ufrj.br.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Coelho-Sampaio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D043170:Collagen Type XVIII / Q000737:chemistry / Q000378:metabolism*; D043169:Endostatins / Q000378:metabolism*; D005110:Extracellular Space / Q000201:enzymology; D031541:Fluorescence Resonance Energy Transfer; D006390:Hemangioendothelioma / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D059748:Proteolysis
chemical_list: D043170:Collagen Type XVIII; D043169:Endostatins; D010455:Peptides; D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex
keywords: Angiogenesis; Collagen XVIII; Endostatin; Protease; Proteasome