ArticleMolecular cancer2014
High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 102 citations in OpenAlex.
- Integrated multi-omics analysis of neutrophil extracellular trap-related genes in renal cell carcinoma using bioinformatics and machine learning.Discover oncology · 2026Article
- Rosy Cells with a Rocky Core: Low-Grade Oncocytic Tumor with Osseous Metaplasia.Journal of kidney cancer and VHL · 2026Article
- Targeting TRPV6/CXCR4 complexes prevents castration-resistant prostate cancer metastasis to the bone.Signal transduction and targeted therapy · 2025Article
- The role of calcium signaling in organotropic metastasis of cancer.Acta pharmacologica Sinica · 2025Review
- Exploring molecular and cellular mechanisms of Pre-Metastatic niche in renal cell carcinoma.Molecular cancer · 2025Review
- Cancer metastasis: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2025Review
- Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop.Experimental & molecular medicine · 2025Article
- New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities.International journal of cancer · 2025Review
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Practical management of renal cell carcinoma: integrating current approaches with advances in bone metastasis treatment.EFORT open reviews · 2024Review
- NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.Journal of cellular and molecular medicine · 2024Article
- Identification of ATP6V0A4 as a potential biomarker in renal cell carcinoma using integrated bioinformatics analysis.Oncology letters · 2023Article
- Article
- Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma.BMC urology · 2023Article
- PECAM1 plays a role in the pathogenesis and treatment of bone metastases.Frontiers in genetics · 2023Article
- Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway.Journal of cell communication and signaling · 2022Article
- Management of Long Bones Metastatic Disease: Concepts That We All Know but Not Always Remember.Orthopedic research and reviews · 2022Review
- Liquid biopsies in primary and secondary bone cancers.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Roles of calcium signaling in cancer metastasis to bone.Exploration of targeted anti-tumor therapy · 2022Review
- Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules.
methodsOur analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 μM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot.
resultsThe expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells.
conclusionsOur results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.