Estrogen receptors in breast and bone: from virtue of remodeling to vileness of metastasis

Bone metastasis is a prominent cause of morbidity and mortality in cancer. High rates of bone colonization in breast cancer, especially in the subtype expressing estrogen receptors (ERs), suggest tissue-specific proclivities for metastatic tumor formation. The mechanisms behind this subtype-specific...

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Bibliographic Details
Published in:Oncogene 2017-08, Vol.36 (32), p.4527-4537
Main Authors: Bado, I, Gugala, Z, Fuqua, S A W, Zhang, X H-F
Format: Article
Language:English
Subjects:
Bone cancer
Bone Development
Bone Neoplasms - metabolism
Bone Neoplasms - secondary
Bone Remodeling
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer metastasis
Care and treatment
Colonization
Complications and side effects
Development and progression
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen Receptor beta - genetics
Estrogen Receptor beta - metabolism
Estrogen receptors
Estrogens
Female
Genetic aspects
Health aspects
Homeostasis
Humans
Metastases
Metastasis
Microenvironments
Morbidity
Osteoblasts
Osteoblasts - metabolism
Osteoclasts
Osteoclasts - metabolism
Stromal Cells - metabolism
Tropism
Tumor Microenvironment - immunology
Tumors
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Summary:Bone metastasis is a prominent cause of morbidity and mortality in cancer. High rates of bone colonization in breast cancer, especially in the subtype expressing estrogen receptors (ERs), suggest tissue-specific proclivities for metastatic tumor formation. The mechanisms behind this subtype-specific organ-tropism remains largely elusive. Interestingly, as the major driver of ER+ breast cancer, ERs also have important roles in bone development and homeostasis. Thus, any agents targeting ER will also inevitably affect the microenvironment, which involves the osteoblasts and osteoclasts. Yet, how such microenvironmental effects are integrated with direct therapeutic responses of cancer cells remain poorly understood. Recent findings on ER mutations, especially their enrichment in bone metastasis, raised even more provocative questions on the role of ER in cancer-bone interaction. In this review, we evaluate the importance of ERs in bone metastasis and discuss new avenues of investigation for bone metastasis treatment based on current knowledge.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2017.94