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dc.contributor.authorJones, Marci D.
dc.contributor.authorLiu, Julie C.
dc.contributor.authorBarthel, Thomas K.
dc.contributor.authorHussain, Sadiq
dc.contributor.authorLovria, Erik
dc.contributor.authorCheng, Dengfeng
dc.contributor.authorSchoonmaker, Jesse A.
dc.contributor.authorMulay, Sudhanshu
dc.contributor.authorAyers, David C.
dc.contributor.authorBouxsein, Mary L.
dc.contributor.authorStein, Gary S.
dc.contributor.authorMukherjee, Siddhartha
dc.contributor.authorLian, Jane B.
dc.date2022-08-11T08:10:57.000
dc.date.accessioned2022-08-23T17:26:25Z
dc.date.available2022-08-23T17:26:25Z
dc.date.issued2010-09-17
dc.date.submitted2011-01-11
dc.identifier.citationClin Cancer Res. 2010 Oct 15;16(20):4978-89. Epub 2010 Sep 15. <a href="http://dx.doi.org/10.1158/1078-0432.CCR-09-3293">Link to article on publisher's site</a>
dc.identifier.issn1078-0432 (Linking)
dc.identifier.doi10.1158/1078-0432.CCR-09-3293
dc.identifier.pmid20843837
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49632
dc.description.abstractPURPOSE: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. EXPERIMENTAL DESIGN: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth. RESULTS: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone. CONCLUSION: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20843837&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1158/1078-0432.CCR-09-3293
dc.subjectProtease Inhibitors
dc.subjectBoronic Acids
dc.subjectPyrazines
dc.subjectBreast Neoplasms
dc.subjectOsteolysis
dc.subjectCell Biology
dc.titleA proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes
dc.typeJournal Article
dc.source.journaltitleClinical cancer research : an official journal of the American Association for Cancer Research
dc.source.volume16
dc.source.issue20
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/6
dc.identifier.contextkey1724046
html.description.abstract<p>PURPOSE: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease.</p> <p>EXPERIMENTAL DESIGN: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth.</p> <p>RESULTS: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone.</p> <p>CONCLUSION: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease.</p>
dc.identifier.submissionpathstein/6
dc.contributor.departmentDepartment of Orthopedics and Physical Rehabilitation
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages4978-89


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