Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice.
Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3772030?pdf=render |
| _version_ | 1819237745228251136 |
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| author | Laura S Gregory Wilson Choi Leslie Burke Judith A Clements |
| author_facet | Laura S Gregory Wilson Choi Leslie Burke Judith A Clements |
| author_sort | Laura S Gregory |
| collection | DOAJ |
| description | Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients. |
| first_indexed | 2024-12-23T13:25:13Z |
| format | Article |
| id | doaj.art-d729da9d31a340a7a47666a520fdc9d6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T13:25:13Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-d729da9d31a340a7a47666a520fdc9d62022-12-21T17:45:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e6810310.1371/journal.pone.0068103Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice.Laura S GregoryWilson ChoiLeslie BurkeJudith A ClementsBone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.http://europepmc.org/articles/PMC3772030?pdf=render |
| spellingShingle | Laura S Gregory Wilson Choi Leslie Burke Judith A Clements Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. PLoS ONE |
| title | Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. |
| title_full | Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. |
| title_fullStr | Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. |
| title_full_unstemmed | Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. |
| title_short | Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice. |
| title_sort | breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice |
| url | http://europepmc.org/articles/PMC3772030?pdf=render |
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