We are upgrading the repository! A content freeze is in effect until December 6, 2024. New submissions or changes to existing items will not be allowed during this period. All content already published will remain publicly available for searching and downloading. Updates will be posted in the Website Upgrade 2024 FAQ in the sidebar Help menu. Reach out to escholarship@umassmed.edu with any questions.
A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes
Authors
Jones, Marci D.Liu, Julie C.
Barthel, Thomas K.
Hussain, Sadiq
Lovria, Erik
Cheng, Dengfeng
Schoonmaker, Jesse A.
Mulay, Sudhanshu
Ayers, David C.
Bouxsein, Mary L.
Stein, Gary S.
Mukherjee, Siddhartha
Lian, Jane B.
UMass Chan Affiliations
Department of Orthopedics and Physical RehabilitationDepartment of Cell Biology
Document Type
Journal ArticlePublication Date
2010-09-17
Metadata
Show full item recordAbstract
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. 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.Source
Clin Cancer Res. 2010 Oct 15;16(20):4978-89. Epub 2010 Sep 15. Link to article on publisher's siteDOI
10.1158/1078-0432.CCR-09-3293Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49632PubMed ID
20843837Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-09-3293