Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma

Frees, Sebastian; Breuksch, Ines; Haber, Tobias; Bauer, Horst; Chávez-Muñoz, Claudia; Raven, Peter A.; Moskalev, Igor; ́Costa, Ninadh D; Tan, Zheng; Daugaard, Mads; Thüroff, Joachim W.; Haferkamp, Axel; Prawitt, Dirk; So, Alan; Brenner, Walburgis

doi:10.18632/oncotarget.24607

Cited by 20 publications

(19 citation statements)

References 47 publications

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“… 115 A recent study found that CaSR overexpression increased the adhesion, migration, and proliferation of RCC cells in a calcium-dependent manner, indicating that cellular calcium might enhance the metastatic behavior of RCC via CaSR. 116 Similar findings were reported in breast cancer cells in which the overexpression of CaSR was correlated with an increase in osteolytic potential. 117 …”

Section: Osteolytic and Osteoblastic Bone Metastasissupporting

confidence: 77%

Molecular mechanisms and clinical management of cancer bone metastasis

et al. 2020

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As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the current understanding of the mechanism of bone metastases. Based on the general process of bone metastases, we specifically highlight the complex crosstalk between tumor cells and the bone microenvironment and the current management of cancer bone metastases.

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Section: Osteolytic and Osteoblastic Bone Metastasissupporting

confidence: 77%

Molecular mechanisms and clinical management of cancer bone metastasis

et al. 2020

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“…In vitro , activation of the CaSR with Ca 2+ or positive allosteric modulator increased PTHrP secretion by BrCa cells [ 26 , 33 ]. Frees et al reported that CaSR antagonist NPS 2143 was able to reverse Ca 2+ -induced increase in cell adhesion, migration and proliferation in renal carcinoma cells transfected with the CaSR plasmid [ 73 ]. However, the effects of CaSR antagonist on CaSR-mediated BrCa bone metastases and osteolytic bone lesions have not been reported yet.…”

Section: Targeting the Pth1r And Casr Signaling For Prevention Of mentioning

confidence: 99%

PTH1R-CaSR Cross Talk: New Treatment Options for Breast Cancer Osteolytic Bone Metastases

Yang

Wang

2018

International Journal of Endocrinology

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Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth. Both the type 1 PTH receptor (PTH1R) and extracellular calcium-sensing receptor (CaSR) participate in the vicious cycle and influence the skeletal metastatic niche. Thus, this review focuses on how the PTH1R and CaSR signaling pathways interact and contribute to the pathogenesis of BrCa bone metastases. The effects of intermittent PTH and allosteric modulators of CaSR for the use of bone-anabolic agents and prevention of BrCa bone metastases constitute a proof of principle for therapeutic consideration. Understanding the interplay between PTH1R and CaSR signaling in the development of BrCa bone metastases could lead to a novel therapeutic approach to control both osteolysis and tumor burden in the bone.

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“…Very recently, their lab also implicated the receptor in promoting bone metastases in mice, using 786-O (RCC) cells with stably transfected CaSR gene. NPS-2143 was able to inhibit the phosphorylation of SHC, AKT, ERK, JNK and p90RSK in response to high Ca 2+ in these transfected cells (100).…”

Section: Calcilytics and Cancermentioning

confidence: 81%