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Type: Artigo de periódico
Title: Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor-Bone Microenvironment
Author: Bruni-Cardoso, A
Johnson, LC
Vessella, RL
Peterson, TE
Lynch, CC
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 histo-morphometry. 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-A164; 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. Mol Cancer Res; 8(4); 459-70. (C) 2010 AACR.
Country: EUA
Editor: Amer Assoc Cancer Research
Citation: Molecular Cancer Research. Amer Assoc Cancer Research, v. 8, n. 4, n. 459, n. 470, 2010.
Rights: fechado
Identifier DOI: 10.1158/1541-7786.MCR-09-0445
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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