Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma
Bibliographic record
Abstract
// Sebastian Frees 1, 2, * , Ines Breuksch 3, * , Tobias Haber 2 , Heide-Katharina Bauer 3 , Claudia Chavez-Munoz 1 , Peter Raven 1 , Igor Moskalev 1 , Ninadh D´Costa 1 , Zheng Tan 1 , Mads Daugaard 1 , Joachim W. Thüroff 2, 4 , Axel Haferkamp 2 , Dirk Prawitt 5 , Alan So 1 and Walburgis Brenner 2, 3 1 Department of Urologic Sciences, University of British Columbia, Vancouver Prostate Centre, British Columbia, Canada 2 Department of Urology, Johannes Gutenberg University Medical Center, Mainz, Germany 3 Department of Gynecology, Johannes Gutenberg University Medical Center, Mainz, Germany 4 Current address: Department of Urology, University Clinic Mannheim, Mannheim, Germany 5 Department of Pediatrics, Johannes Gutenberg University Medical Center, Mainz, Germany * These authors contributed equally to this work Correspondence to: Sebastian Frees, email: sebastian.frees@unimedizin-mainz.de Keywords: renal cell carcinoma; calcium-sensing receptor; bone metastases, metastasis; kidney cancer Received: December 21, 2017 Accepted: February 25, 2018 Epub: March 02, 2018 Published: March 20, 2018 ABSTRACT Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC). The calcium-sensing receptor (CaSR) has been associated with bone metastasis in several different malignancies. We analyzed the impact of CaSR in bone metastasis in RCC in vitro and in vivo . The RCC cell line 786-O was stably transfected with the CaSR gene and treated with calcium alone or in combination with the CaSR antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent signaling molecules were analyzed. Calcium treated CaSR -transfected 768-O cells showed an increased adhesion to endothelial cells and the extracellular matrix components fibronectin and collagen I, but not to collagen IV. The chemotactic cell migration and proliferation was also induced by calcium. The activity of SHC, AKT, ERK, P90RSK and JNK were enhanced after calcium treatment of CaSR -transfected cells. These effects were abolished by NPS2143. Development of bone metastasis was evaluated in vivo in a mouse model. Intracardiac injection of CaSR-transfected 768-O cells showed an increased rate of bone metastasis. The results indicate CaSR as an important component in the mechanism of bone metastasis in RCC. Therefore, targeting CaSR might be beneficial in patients with bone metastatic RCC with a high CaSR expression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".