Please use this identifier to cite or link to this item:
Type: Artigo de periódico
Title: Osteoclast-derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis In The Prostate Tumor-bone Microenvironment.
Author: Bruni-Cardoso, Alexandre
Johnson, Lindsay C
Vessella, Robert L
Peterson, Todd E
Lynch, Conor C
Abstract: In human prostate to bone metastases and in a novel rodent model that recapitulates prostate tumor-induced osteolytic and osteogenic responses, we found that osteoclasts are a major source of the proteinase, matrix metalloproteinase (MMP)-9. Because MMPs are important mediators of tumor-host communication, we tested the effect of host-derived MMP-9 on prostate tumor progression in the bone. To this end, immunocompromised mice that were wild-type or null for MMP-9 received transplants of osteolytic/osteogenic-inducing prostate adenocarcinoma tumor tissue to the calvaria. Surprisingly, we found that that host MMP-9 significantly contributed to prostate tumor growth without affecting prostate tumor-induced osteolytic or osteogenic change as determined by microcomputed tomography, microsingle-photon emission computed tomography, and histomorphometry. Subsequent studies aimed at delineating the mechanism of MMP-9 action on tumor growth focused on angiogenesis because MMP-9 and osteoclasts have been implicated in this process. We observed (a) significantly fewer and smaller blood vessels in the MMP-9 null group by CD-31 immunohistochemistry; (b) MMP-9 null osteoclasts had significantly lower levels of bioavailable vascular endothelial growth factor-A(164); and (c) using an aorta sprouting assay, conditioned media derived from wild-type osteoclasts was significantly more angiogenic than conditioned media derived from MMP-9 null osteoclasts. In conclusion, these studies show that osteoclast-derived MMP-9 affects prostate tumor growth in the bone microenvironment by contributing to angiogenesis without altering prostate tumor-induced osteolytic or osteogenic changes.
Subject: Adenocarcinoma
Cell Proliferation
Cells, Cultured
Culture Media, Conditioned
Graft Survival
Matrix Metalloproteinase 9
Mice, Inbred C57bl
Mice, Knockout
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Neovascularization, Pathologic
Prostatic Neoplasms
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Citation: Molecular Cancer Research : Mcr. v. 8, n. 4, p. 459-70, 2010-Apr.
Rights: fechado
Identifier DOI: 10.1158/1541-7786.MCR-09-0445
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
pmed_20332212.pdf2.06 MBAdobe PDFView/Open

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