The Endosteal Niche in Breast Cancer Bone Metastasis
The establishment of bone metastasis remains one of the most frequent complications of patients suffering from advanced breast cancer. Patients with bone metastases experience high morbidity and mortality caused by excessive, tumor-induced and osteoclast-mediated bone resorption. Anti-resorptive tre...
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doaj-dbc0e9e155fe4c6987efa2bc35839a282020-11-25T00:31:10ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-03-011010.3389/fonc.2020.00335521337The Endosteal Niche in Breast Cancer Bone MetastasisMarie-Therese Haider0Daniel J. Smit1Hanna Taipaleenmäki2Molecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMolecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyThe establishment of bone metastasis remains one of the most frequent complications of patients suffering from advanced breast cancer. Patients with bone metastases experience high morbidity and mortality caused by excessive, tumor-induced and osteoclast-mediated bone resorption. Anti-resorptive treatments, such as bisphosphonates, are available to ease skeletal related events including pain, increased fracture risk, and hypercalcemia. However, the disease remains incurable and 5-year survival rates for these patients are below 25%. Within the bone, disseminated breast cancer cells localize in “metastatic niches,” special microenvironments that are thought to regulate cancer cell colonization and dormancy as well as tumor progression and subsequent development into overt metastases. Precise location and composition of this “metastatic niche” remain poorly defined. However, it is thought to include an “endosteal niche” that is composed of key bone cells that are derived from both, hematopoietic stem cells (osteoclasts), and mesenchymal stromal cells (osteoblasts, fibroblasts, adipocytes). Our knowledge of how osteoclasts drive the late stage of the disease is well-established. In contrast, much less is known about the interaction between osteogenic cells and disseminated tumor cells prior to the initiation of the osteolytic phase. Recent studies suggest that mesenchymal-derived cells, including osteoblasts and fibroblasts, play a key role during the early stages of breast cancer bone metastasis such as tumor cell homing, bone marrow colonization, and tumor cell dormancy. Hence, elucidating the interactions between breast cancer cells and mesenchymal-derived cells that drive metastasis progression could provide novel therapeutic approaches and targets to treat breast cancer bone metastasis. In this review we discuss evidences reporting the interaction between tumor cells and endosteal niche cells during the early stages of breast cancer bone metastasis, with a particular focus on mesenchymal-derived osteoblasts and fibroblasts.https://www.frontiersin.org/article/10.3389/fonc.2020.00335/fullbreast cancerbone metastasesendosteal nichemicroenvironmentosteoblastfibroblast |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marie-Therese Haider Daniel J. Smit Hanna Taipaleenmäki |
spellingShingle |
Marie-Therese Haider Daniel J. Smit Hanna Taipaleenmäki The Endosteal Niche in Breast Cancer Bone Metastasis Frontiers in Oncology breast cancer bone metastases endosteal niche microenvironment osteoblast fibroblast |
author_facet |
Marie-Therese Haider Daniel J. Smit Hanna Taipaleenmäki |
author_sort |
Marie-Therese Haider |
title |
The Endosteal Niche in Breast Cancer Bone Metastasis |
title_short |
The Endosteal Niche in Breast Cancer Bone Metastasis |
title_full |
The Endosteal Niche in Breast Cancer Bone Metastasis |
title_fullStr |
The Endosteal Niche in Breast Cancer Bone Metastasis |
title_full_unstemmed |
The Endosteal Niche in Breast Cancer Bone Metastasis |
title_sort |
endosteal niche in breast cancer bone metastasis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-03-01 |
description |
The establishment of bone metastasis remains one of the most frequent complications of patients suffering from advanced breast cancer. Patients with bone metastases experience high morbidity and mortality caused by excessive, tumor-induced and osteoclast-mediated bone resorption. Anti-resorptive treatments, such as bisphosphonates, are available to ease skeletal related events including pain, increased fracture risk, and hypercalcemia. However, the disease remains incurable and 5-year survival rates for these patients are below 25%. Within the bone, disseminated breast cancer cells localize in “metastatic niches,” special microenvironments that are thought to regulate cancer cell colonization and dormancy as well as tumor progression and subsequent development into overt metastases. Precise location and composition of this “metastatic niche” remain poorly defined. However, it is thought to include an “endosteal niche” that is composed of key bone cells that are derived from both, hematopoietic stem cells (osteoclasts), and mesenchymal stromal cells (osteoblasts, fibroblasts, adipocytes). Our knowledge of how osteoclasts drive the late stage of the disease is well-established. In contrast, much less is known about the interaction between osteogenic cells and disseminated tumor cells prior to the initiation of the osteolytic phase. Recent studies suggest that mesenchymal-derived cells, including osteoblasts and fibroblasts, play a key role during the early stages of breast cancer bone metastasis such as tumor cell homing, bone marrow colonization, and tumor cell dormancy. Hence, elucidating the interactions between breast cancer cells and mesenchymal-derived cells that drive metastasis progression could provide novel therapeutic approaches and targets to treat breast cancer bone metastasis. In this review we discuss evidences reporting the interaction between tumor cells and endosteal niche cells during the early stages of breast cancer bone metastasis, with a particular focus on mesenchymal-derived osteoblasts and fibroblasts. |
topic |
breast cancer bone metastases endosteal niche microenvironment osteoblast fibroblast |
url |
https://www.frontiersin.org/article/10.3389/fonc.2020.00335/full |
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