Osteoclast-derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis In The Prostate Tumor-bone Microenvironment.

dc.creatorBruni-Cardoso, Alexandre
dc.creatorJohnson, Lindsay C
dc.creatorVessella, Robert L
dc.creatorPeterson, Todd E
dc.creatorLynch, Conor C
dc.date2010-Apr
dc.date2015-11-27T13:17:41Z
dc.date2015-11-27T13:17:41Z
dc.date.accessioned2018-03-29T01:10:35Z
dc.date.available2018-03-29T01:10:35Z
dc.identifierMolecular Cancer Research : Mcr. v. 8, n. 4, p. 459-70, 2010-Apr.
dc.identifier1557-3125
dc.identifier10.1158/1541-7786.MCR-09-0445
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/20332212
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/198774
dc.identifier20332212
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1299007
dc.descriptionIn 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.
dc.description8
dc.description459-70
dc.languageeng
dc.relationMolecular Cancer Research : Mcr
dc.relationMol. Cancer Res.
dc.rightsfechado
dc.rights(c) 2010 AACR.
dc.sourcePubMed
dc.subjectAdenocarcinoma
dc.subjectAnimals
dc.subjectCell Proliferation
dc.subjectCells, Cultured
dc.subjectCulture Media, Conditioned
dc.subjectGraft Survival
dc.subjectMale
dc.subjectMatrix Metalloproteinase 9
dc.subjectMice
dc.subjectMice, Inbred C57bl
dc.subjectMice, Knockout
dc.subjectNeoplasm Invasiveness
dc.subjectNeoplasm Metastasis
dc.subjectNeoplasm Transplantation
dc.subjectNeovascularization, Pathologic
dc.subjectOsteoclasts
dc.subjectOsteogenesis
dc.subjectProstatic Neoplasms
dc.subjectRats
dc.subjectSkull
dc.subjectTumor Cells, Cultured
dc.subjectVascular Endothelial Growth Factor A
dc.titleOsteoclast-derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis In The Prostate Tumor-bone Microenvironment.
dc.typeArtículos de revistas


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