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Apo2l/Tumor necrosis factor-related apoptosis-inducing ligand prevents breast cancer-induced bone destruction in a mouse model.
Cancer Res. 2006 May 15; 66(10):5363-70.CR

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.

Authors+Show Affiliations

Department of Orthopaedics, Royal Adelaide Hospital, Adelaide University, Adelaide, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16707463

Citation

Thai, Le Minh, et al. "Apo2l/Tumor Necrosis Factor-related Apoptosis-inducing Ligand Prevents Breast Cancer-induced Bone Destruction in a Mouse Model." Cancer Research, vol. 66, no. 10, 2006, pp. 5363-70.
Thai le M, Labrinidis A, Hay S, et al. Apo2l/Tumor necrosis factor-related apoptosis-inducing ligand prevents breast cancer-induced bone destruction in a mouse model. Cancer Res. 2006;66(10):5363-70.
Thai, l. e. . M., Labrinidis, A., Hay, S., Liapis, V., Bouralexis, S., Welldon, K., Coventry, B. J., Findlay, D. M., & Evdokiou, A. (2006). Apo2l/Tumor necrosis factor-related apoptosis-inducing ligand prevents breast cancer-induced bone destruction in a mouse model. Cancer Research, 66(10), 5363-70.
Thai le M, et al. Apo2l/Tumor Necrosis Factor-related Apoptosis-inducing Ligand Prevents Breast Cancer-induced Bone Destruction in a Mouse Model. Cancer Res. 2006 May 15;66(10):5363-70. PubMed PMID: 16707463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apo2l/Tumor necrosis factor-related apoptosis-inducing ligand prevents breast cancer-induced bone destruction in a mouse model. AU - Thai,Le Minh, AU - Labrinidis,Agatha, AU - Hay,Shelley, AU - Liapis,Vasilios, AU - Bouralexis,Steve, AU - Welldon,Katie, AU - Coventry,Brendon J, AU - Findlay,David M, AU - Evdokiou,Andreas, PY - 2006/5/19/pubmed PY - 2006/7/19/medline PY - 2006/5/19/entrez SP - 5363 EP - 70 JF - Cancer research JO - Cancer Res VL - 66 IS - 10 N2 - 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/16707463/Apo2l/Tumor_necrosis_factor_related_apoptosis_inducing_ligand_prevents_breast_cancer_induced_bone_destruction_in_a_mouse_model_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16707463 DB - PRIME DP - Unbound Medicine ER -