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Type: Journal article
Title: Apo21/tumor necrosis factor-related apoptosis-inducing ligand prevents breast cancer-induced bone destruction in a mouse model
Author: Thai, L.
Labrinidis, A.
Hay, S.
Liapis, V.
Bouralexis, S.
Welldon, K.
Coventry, B.
Findlay, D.
Evdokiou, A.
Citation: Cancer Research, 2006; 66(10):5363-5370
Publisher: Amer Assoc Cancer Research
Issue Date: 2006
ISSN: 0008-5472
Statement of
Le Minh Thai, Agatha Labrinidis, Shelley Hay, Vasilios Liapis, Steve Bouralexis, Katie Welldon, Brendon J. Coventry, David M. Findlay and Andreas Evdokiou
Abstract: Breast cancer is the most common carcinoma that metastasizes to bone. To examine the efficacy of recombinant soluble Apo2 ligand (Apo2L)/tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) against breast cancer growth in bone, we established a mouse model in which MDA-MB-231 human breast cancer cells were transplanted directly into the marrow cavity of the tibiae of athymic nude mice producing osteolytic lesions in the area of injection. All vehicle-treated control animals developed large lesions that established in the marrow cavity, eroded the cortical bone, and invaded the surrounding soft tissue, as assessed by radiography, micro-computed tomography, and histology. In contrast, animals treated with recombinant soluble Apo2L/TRAIL showed significant conservation of the tibiae, with 85% reduction in osteolysis, 90% reduction in tumor burden, and no detectable soft tissue invasion. Tumor cells explanted from Apo2L/TRAIL–treated animals were significantly more resistant to the effects of Apo2L/TRAIL when compared with the cells explanted from the vehicle-treated control animals, suggesting that prolonged treatment with Apo2/TRAIL in vivo selects for a resistant phenotype. However, such resistance was readily reversed when Apo2L/TRAIL was used in combination with clinically relevant chemotherapeutic drugs, including taxol, etoposide, doxorubicin, cisplatin, or the histone deacetylase inhibitor suberoylanilide hydroxamic acid. These studies show for the first time that Apo2L/TRAIL can prevent breast cancer–induced bone destruction and highlight the potential of this ligand for the treatment of metastatic breast cancer in bone.
Keywords: Cell Line, Tumor; Animals; Humans; Mice; Mice, Nude; Breast Neoplasms; Osteolysis; Disease Models, Animal; Tumor Necrosis Factor-alpha; Membrane Glycoproteins; Green Fluorescent Proteins; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Xenograft Model Antitumor Assays; Apoptosis; Cell Growth Processes; Drug Synergism; Female; Apoptosis Regulatory Proteins; TNF-Related Apoptosis-Inducing Ligand
Description: © 2006 American Association for Cancer Research
RMID: 0020062583
DOI: 10.1158/0008-5472.CAN-05-4386
Appears in Collections:Surgery publications

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