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Int. J. Mol. Sci. 2016, 17(10), 1764;

What Is Breast in the Bone?

Department of Biological Sciences and Arnie Charbonneau Cancer Institute, 2500 University Dr, NW, University of Calgary, Calgary, AB T2N 1N4, Canada
Author to whom correspondence should be addressed.
Academic Editor: Maria Alfonsina Desiderio
Received: 1 September 2016 / Revised: 11 October 2016 / Accepted: 14 October 2016 / Published: 22 October 2016
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Bone Metastasis)
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The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%–50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural “recycling” of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle. View Full-Text
Keywords: bone metastasis; prolactin; prolactin receptor; breast cancer; Sonic Hedgehog; osteoclast; osteolytic metastasis; osteoclastogenesis bone metastasis; prolactin; prolactin receptor; breast cancer; Sonic Hedgehog; osteoclast; osteolytic metastasis; osteoclastogenesis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Shemanko, C.S.; Cong, Y.; Forsyth, A. What Is Breast in the Bone? Int. J. Mol. Sci. 2016, 17, 1764.

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