Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/198774
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
Animals
Cell Proliferation
Cells, Cultured
Culture Media, Conditioned
Graft Survival
Male
Matrix Metalloproteinase 9
Mice
Mice, Inbred C57bl
Mice, Knockout
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Neovascularization, Pathologic
Osteoclasts
Osteogenesis
Prostatic Neoplasms
Rats
Skull
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Rights: fechado
Identifier DOI: 10.1158/1541-7786.MCR-09-0445
Address: http://www.ncbi.nlm.nih.gov/pubmed/20332212
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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