What Is Breast in the Bone?

Abstract

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.

Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway

“…Besides the osteoclasts, breast cancer cells can also interact with the osteoblasts to support osteoclast formation [ 22 ]. Breast cancer cells increase the expression of the osteoclast differentiation factors, M-CSF and RANKL, and decrease OPG levels in the osteoblasts, which could result in osteoclastogenesis [ 6 ]. Therefore, molecular targeting of cancer-mediated osteoclastogenesis or restoring the balance between the osteoblast-osteoclast interactions can reduce bone destruction.…”

“…The metastasis of breast cancer to the bone begins with the initiation of bone demolition, entry of malignant cells into the bone marrow, and a subsequent increase in osteolysis [ 6 ]. Tumor cells, which reach the bone microenvironment, secrete factors, such as PTHrP, which stimulate the osteoblasts to secrete RANKL, IL-8, IL-6, and IL-1.…”

“…In breast cancer bone metastases, although local bone-forming and osteoblastic lesions are observed, the dominant bone lesions are destructive and osteolytic [ 5 ]. Breast cancer cells secrete factors that act on the pre-osteoclasts, osteoblasts, and bone stromal cells to stimulate the production of mature osteoclasts, which degrade the bone, resulting in the release of growth factors that stimulate breast cancer cell proliferation and perpetuate a vicious osteolytic cycle [ 6 ]. Osteoclasts are the host cells responsible for bone resorption in such pathological situations.…”

Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma

“…In the case of the ALN-OSILs, the obtained data clearly shows that the monoanionic OSILs elicited lower cytotoxicity than the corresponding dianionic versions for all cell types. Regarding Breast and lung cancers are often associated with bone osteolytic metastases [27][28][29] and also osteosarcoma, which are usually caused by disturbances in bone metabolism and increases in bone turnover rates [6,30,31]. Thus, the development of OSILs with high cytotoxicity towards the tested cancer cell types and containing an anti-resorbing molecule (alendronate) may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.…”

Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis

“…Bone metastases are typically incurable and 5-year survival rate of patients with bone-metastatic relapse drops to < 10% 1 , 2 . Most of breast cancer metastasis to bone is osteolytic (bone destructive) 3 , 4 and encompass severe morbidities, including pathologic fractures, pain, and hypercalcemia 1 , 5 , 6 . Therefore, deeper understanding of the mechanisms that enable bone metastatic relapse is an urgent medical need, in order to inhibit or prevent this devastating pathology.…”