The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability

Wang, Hai; Tian, Lin; Li, Jun; Goldstein, Amit; Bado, Igor; Zhang, Weijie; Arenkiel, Benjamin R.; Li, Zonghai; Meng, Yang; Du, Shiyu; Zhao, Hong; Rowley, David R.; Wong, Stephen T.C.; Gugala, Zbigniew; Zhang, Xiang H.-F.

doi:10.1016/j.ccell.2018.10.002

Cited by 106 publications

(115 citation statements)

References 72 publications

(94 reference statements)

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“…Calcium flux, for instance, has been identified as a mechanism of crosstalk between the osteogenic niche and cancer cells, which promotes the progression of bone metastasis. 236 Another example involves patients with postpartum breast cancer, who are at elevated risk for liver metastasis. 237 The identification of the "weaning-induced liver involution," which establishes a metastatic microenvironment, may account, in part, for the poor prognosis of patients with postpartum breast cancer.…”

Section: Extravasationmentioning

confidence: 99%

Molecular principles of metastasis: a hallmark of cancer revisited

Fares

Khachfe

et al. 2020

Sig Transduct Target Ther

1,418

935

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Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process. The invading tumor cell, on its way to the target site, interacts with other proteins and cells. Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity. Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges, settle, and colonize. These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. In this review, the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.

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Section: Extravasationmentioning

confidence: 99%

Molecular principles of metastasis: a hallmark of cancer revisited

Fares

Khachfe

et al. 2020

Sig Transduct Target Ther

1,418

935

View full text Add to dashboard Cite

show abstract

“…In particular, the abundant calcium in the bone matrix can attract the calcium-sensing receptor-expressing breast cancer cells to the bone. Furthermore, Wang et al (2018) showed that the increased intracellular calcium concentration in metastatic breast cancer cells induced by connexin 43 can disturb the osteogenic niche and promote survival (Waning et al, 2019). Furthermore, the bone microenvironment promotes breast cancer cells to transit to a migratory phenotype with new malignant capacities.…”

Section: Adhesion and Survivalmentioning

confidence: 99%

RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies

Dang

et al. 2020

Front. Cell Dev. Biol.

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Breast cancer remains one of the most life-threatening tumors affecting women. Most patients with advanced breast cancer eventually develop metastatic diseases, which cause significant morbidity and mortality. Approximately two-thirds of patients with advanced breast cancer exhibit osteolytic-type bone metastasis, which seriously reduce the quality of life. Therefore, development of novel therapeutic strategies for treating breast cancer patients with bone metastasis is urgently required. The "seed and soil" theory, which describes the interaction between the circulating breast cancer cells (seeds) and bone microenvironment (soil), is widely accepted as the mechanism underlying metastasis. Disruption of any step in this cycle might have promising antimetastasis implications. The interaction of receptor activator of nuclear factor-κB ligand (RANKL) and its receptor RANK is fundamental in this vicious cycle and has been shown to be a novel effective therapeutic target. A series of therapeutic strategies have been developed to intervene in this cross-talk. Therefore, in this review, we have systematically introduced the functions of the RANKL/RANK signaling system in breast cancer and discussed related therapeutic strategies.

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“…However, a group of scientists found that intracellular [Ca 2+ ] but not PKC was required for S1P‐induced p42/44 MAPK activation, indicating that PKC exerts a proliferative effect without activating MAPK 32 . Calcium is found mainly in bone, and intracellular [Ca 2+ ] plays an essential role in bone metabolism and metastasis 33‐35 . Therefore, the involvement of the calcium signalling pathway in S1P‐induced osteoblast proliferation significantly improves our understanding of the function of [Ca 2+ ] in bone homeostasis.…”

Section: The Function Of S1p On Osteoclasts and Osteoblastsmentioning

confidence: 99%

Sphingosine‐1‐phosphate (S1P) receptors: Promising drug targets for treating bone‐related diseases

Zhang

Dong

et al. 2020

J Cellular Molecular Medi

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Bone is regarded as a highly dynamic tissue that constantly undergoes cycles of bone resorption and bone formation. The whole cycle is divided into three phases: (a) the interaction of osteoclast precursors (OCPs) and osteoblasts (OBs) on the bone surface, including OCP recruitment, RANKL-RANK binding and adhesion to the bone surface; (b) the differentiation of osteoblast precursors (OBPs) is facilitated by various cytokines from mature osteoclasts; and (c) the apoptosis of osteoclasts (OCs), as well as mineralization of the bone matrix. 1 During these OCPs and OBPs migrate to the bone surface, and various coupling factors, such as receptor activator of nuclear factor-κ B ligand (RANKL), have a dramatic influence on the bone regeneration cycle. Currently, S1P has been recognized to participate in this remodelling cycle, suggesting its significance in bone pathology.Sphingosine-1-phosphate (S1P) is a natural bioactive lipid molecule and a common first or second messenger in the cardiovascular and immune systems. 2,3 At present, research on the role of S1P in the Abstract Sphingosine-1-phosphate (S1P) is a natural bioactive lipid molecule and a common first or second messenger in the cardiovascular and immune systems. By binding with its receptors, S1P can serve as mediator of signalling during cell migration, differentiation, proliferation and apoptosis. Although the predominant role of S1P in bone regeneration has been noted in many studies, this role is not as well-known as its roles in the cardiovascular and immune systems. In this review, we summarize previous research on the role of S1P receptors (S1PRs) in osteoblasts and osteoclasts. In addition, S1P is regarded as a bridge between bone resorption and formation, which brings hope to patients with bone-related diseases. Finally, we discuss S1P and its receptors as therapeutic targets for treating osteoporosis, inflammatory osteolysis and bone metastasis based on the biological effects of S1P in osteoclastic/osteoblastic cells, immune cells and tumour cells. K E Y W O R D Scancer-related bone metastasis, inflammatory osteolysis, osteoporosis, S1P receptors

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The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability

Cited by 106 publications

References 72 publications

Molecular principles of metastasis: a hallmark of cancer revisited

Molecular principles of metastasis: a hallmark of cancer revisited

RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies

Sphingosine‐1‐phosphate (S1P) receptors: Promising drug targets for treating bone‐related diseases

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