Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer
Prostate cancer preferentially metastasizes to bone, which is rich in structural and matricellular proteins capable of altering prostate cancer progression. This study explores the role of the bone stromal matricellular protein SPARC (osteonectin/BM-40) in the progression of bone metastatic prostate...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558611801090 |
| _version_ | 1818806963644923904 |
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| author | N. Patrick McCabe Bethany A. Kerr Maria Madajka Amit Vasanji Tatiana V. Byzova |
| author_facet | N. Patrick McCabe Bethany A. Kerr Maria Madajka Amit Vasanji Tatiana V. Byzova |
| author_sort | N. Patrick McCabe |
| collection | DOAJ |
| description | Prostate cancer preferentially metastasizes to bone, which is rich in structural and matricellular proteins capable of altering prostate cancer progression. This study explores the role of the bone stromal matricellular protein SPARC (osteonectin/BM-40) in the progression of bone metastatic prostate cancer. Quantification of bone destruction analyzed by micro–computed tomography showed augmented osteoclastic resorption, characterized by decreases in several morphometric bone parameters in SPARC knock out (KO) tibiae harboring RM1 murine prostate cancer cells compared with wild type (WT) animals. Tumor progression stimulated osteoclast formation, which was augmented in SPARC KO mice. In vitro differentiation of SPARC KO osteoclasts indicated accelerated progenitor expansion and formation of tartrate-resistant acid phosphatase–positive osteoclast-like cells with increased resorptive capacity, a mechanism resulting in enhanced tumor-induced bone loss in vivo. Whereas altered bone structure due to SPARC KO played a role in increased osteolysis, the enhanced osteolysis was primarily the result of increased resorption by SPARC KO osteoclasts. Our findings indicate that bone stromal SPARC suppresses tumor-induced bone lesion expansion by limiting osteoclast maturation and function. |
| first_indexed | 2024-12-18T19:18:07Z |
| format | Article |
| id | doaj.art-82de2352c9d64380b19e2e728633c01e |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-18T19:18:07Z |
| publishDate | 2011-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-82de2352c9d64380b19e2e728633c01e2022-12-21T20:56:04ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-01-01131313910.1593/neo.10998Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate CancerN. Patrick McCabe0Bethany A. Kerr1Maria Madajka2Amit Vasanji3Tatiana V. Byzova4Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation Cleveland OH USADepartment of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation Cleveland OH USADepartment of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation Cleveland OH USADepartment of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation Cleveland OH USADepartment of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation Cleveland OH USAProstate cancer preferentially metastasizes to bone, which is rich in structural and matricellular proteins capable of altering prostate cancer progression. This study explores the role of the bone stromal matricellular protein SPARC (osteonectin/BM-40) in the progression of bone metastatic prostate cancer. Quantification of bone destruction analyzed by micro–computed tomography showed augmented osteoclastic resorption, characterized by decreases in several morphometric bone parameters in SPARC knock out (KO) tibiae harboring RM1 murine prostate cancer cells compared with wild type (WT) animals. Tumor progression stimulated osteoclast formation, which was augmented in SPARC KO mice. In vitro differentiation of SPARC KO osteoclasts indicated accelerated progenitor expansion and formation of tartrate-resistant acid phosphatase–positive osteoclast-like cells with increased resorptive capacity, a mechanism resulting in enhanced tumor-induced bone loss in vivo. Whereas altered bone structure due to SPARC KO played a role in increased osteolysis, the enhanced osteolysis was primarily the result of increased resorption by SPARC KO osteoclasts. Our findings indicate that bone stromal SPARC suppresses tumor-induced bone lesion expansion by limiting osteoclast maturation and function.http://www.sciencedirect.com/science/article/pii/S1476558611801090 |
| spellingShingle | N. Patrick McCabe Bethany A. Kerr Maria Madajka Amit Vasanji Tatiana V. Byzova Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer Neoplasia: An International Journal for Oncology Research |
| title | Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer |
| title_full | Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer |
| title_fullStr | Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer |
| title_full_unstemmed | Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer |
| title_short | Augmented Osteolysis in SPARC-Deficient Mice with Bone-Residing Prostate Cancer |
| title_sort | augmented osteolysis in sparc deficient mice with bone residing prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1476558611801090 |
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