title: Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis.
abstract: Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promoting effects by binding to TNF-related apoptosis inducing ligand (TRAIL), thereby preventing induction of apoptosis. However, the in vivo effect of OPG expression by primary breast tumors has not been characterized. We knocked down OPG expression in MDA-MB-231 and MDA-MB-436 human breast cancer cells using shRNA and siRNA to investigate impact on metastasis in the chick embryo model. We observed a reduction in metastasis with OPG knockdown cells. We found that lowering OPG expression did not alter sensitivity to TRAIL-induced apoptosis; however, the OPG knockdown cells had a reduced level of invasion. In association with this we observed reduced expression of the proteases Cathepsin D and Matrix Metalloproteinase-2 upon OPG knockdown, indicating that OPG may promote metastasis via modulation of protease expression and invasion. We conclude that OPG has a metastasis-promoting effect in breast cancer cells.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii.
authors: Michael
authors: M
authors: Weichhaus
authors: Prabu
authors: P
authors: Segaran
authors: Ashleigh
authors: A
authors: Renaud
authors: Dirk
authors: D
authors: Geerts
authors: Linda
authors: L
authors: Connelly
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D056915:DNA Copy Number Variations; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D009362:Neoplasm Metastasis; D053244:Osteoprotegerin / Q000235:genetics*; D063868:Patient Outcome Assessment; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*
chemical_list: D053244:Osteoprotegerin; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; D010447:Peptide Hydrolases
keywords: Breast cancer; TRAIL; metastasis; osteoprotegerin