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Enhanced Bone Metastases in Skeletally Immature Mice

Bone constitutes the most common site of breast cancer metastases either at time of presentation or recurrent disease years after seemingly successful therapy. Bone metastases cause substantial morbidity, including life-threatening spinal cord compression and hypercalcemia. Given the high prevalence...

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Detalles Bibliográficos
Autores principales: Haley, Henry R., Shen, Nathan, Qyli, Tonela, Buschhaus, Johanna M., Pirone, Matthew, Luker, Kathryn E., Luker, Gary D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Grapho Publications, LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035009/
https://www.ncbi.nlm.nih.gov/pubmed/29984313
http://dx.doi.org/10.18383/j.tom.2018.00010
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author Haley, Henry R.
Shen, Nathan
Qyli, Tonela
Buschhaus, Johanna M.
Pirone, Matthew
Luker, Kathryn E.
Luker, Gary D.
author_facet Haley, Henry R.
Shen, Nathan
Qyli, Tonela
Buschhaus, Johanna M.
Pirone, Matthew
Luker, Kathryn E.
Luker, Gary D.
author_sort Haley, Henry R.
collection PubMed
description Bone constitutes the most common site of breast cancer metastases either at time of presentation or recurrent disease years after seemingly successful therapy. Bone metastases cause substantial morbidity, including life-threatening spinal cord compression and hypercalcemia. Given the high prevalence of patients with breast cancer, health-care costs of bone metastases (>$20,000 per episode) impose a tremendous economic burden on society. To investigate mechanisms of bone metastasis, we developed femoral artery injection of cancer cells as a physiologically relevant model of bone metastasis. Comparing young (∼6 weeks), skeletally immature mice to old (∼6 months) female mice with closed physes (growth plates), we showed significantly greater progression of osteolytic metastases in young animals. Bone destruction increased in the old mice following ovariectomy, emphasizing the pathologic consequences of greater bone turnover and net loss. Despite uniform initial distribution of breast cancer cells throughout the hind limb after femoral artery injection, we observed preferential formation of osteolytic bone metastases in the proximal tibia. Tropism for the proximal tibia arises in part because of TGF-β, a cytokine abundant in both physes of skeletally immature mice and matrix of bone in mice of all ages. We also showed that age-dependent effects on osteolytic bone metastases did not occur in male mice with disseminated breast cancer cells in bone. These studies establish a model system to specifically focus on pathophysiology and treatment of bone metastases and underscore the need to match biologic variables in the model to relevant subsets of patients with breast cancer.
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spelling pubmed-60350092018-07-06 Enhanced Bone Metastases in Skeletally Immature Mice Haley, Henry R. Shen, Nathan Qyli, Tonela Buschhaus, Johanna M. Pirone, Matthew Luker, Kathryn E. Luker, Gary D. Tomography Research Articles Bone constitutes the most common site of breast cancer metastases either at time of presentation or recurrent disease years after seemingly successful therapy. Bone metastases cause substantial morbidity, including life-threatening spinal cord compression and hypercalcemia. Given the high prevalence of patients with breast cancer, health-care costs of bone metastases (>$20,000 per episode) impose a tremendous economic burden on society. To investigate mechanisms of bone metastasis, we developed femoral artery injection of cancer cells as a physiologically relevant model of bone metastasis. Comparing young (∼6 weeks), skeletally immature mice to old (∼6 months) female mice with closed physes (growth plates), we showed significantly greater progression of osteolytic metastases in young animals. Bone destruction increased in the old mice following ovariectomy, emphasizing the pathologic consequences of greater bone turnover and net loss. Despite uniform initial distribution of breast cancer cells throughout the hind limb after femoral artery injection, we observed preferential formation of osteolytic bone metastases in the proximal tibia. Tropism for the proximal tibia arises in part because of TGF-β, a cytokine abundant in both physes of skeletally immature mice and matrix of bone in mice of all ages. We also showed that age-dependent effects on osteolytic bone metastases did not occur in male mice with disseminated breast cancer cells in bone. These studies establish a model system to specifically focus on pathophysiology and treatment of bone metastases and underscore the need to match biologic variables in the model to relevant subsets of patients with breast cancer. Grapho Publications, LLC 2018-06 /pmc/articles/PMC6035009/ /pubmed/29984313 http://dx.doi.org/10.18383/j.tom.2018.00010 Text en © 2018 The Authors. Published by Grapho Publications, LLC http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Articles
Haley, Henry R.
Shen, Nathan
Qyli, Tonela
Buschhaus, Johanna M.
Pirone, Matthew
Luker, Kathryn E.
Luker, Gary D.
Enhanced Bone Metastases in Skeletally Immature Mice
title Enhanced Bone Metastases in Skeletally Immature Mice
title_full Enhanced Bone Metastases in Skeletally Immature Mice
title_fullStr Enhanced Bone Metastases in Skeletally Immature Mice
title_full_unstemmed Enhanced Bone Metastases in Skeletally Immature Mice
title_short Enhanced Bone Metastases in Skeletally Immature Mice
title_sort enhanced bone metastases in skeletally immature mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035009/
https://www.ncbi.nlm.nih.gov/pubmed/29984313
http://dx.doi.org/10.18383/j.tom.2018.00010
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