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

Sebastian Frees; Ines Breuksch; Tobias Haber; Heide-Katharina Bauer; Claudia Chavez-Munoz; Peter Raven; Igor Moskalev; Ninadh D´Costa; Zheng Tan; Mads Daugaard; Joachim W. Thüroff; Axel Haferkamp; Dirk Prawitt; Alan So; Walburgis Brenner

doi:10.18632/oncotarget.24607

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

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

Sebastian Frees _, Ines Breuksch, Tobias Haber, Heide-Katharina Bauer, Claudia Chavez-Munoz, Peter Raven, Igor Moskalev, Ninadh D´Costa, Zheng Tan, Mads Daugaard, Joachim W. Thüroff, Axel Haferkamp, Dirk Prawitt, Alan So and Walburgis Brenner

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2018; 9:15766-15779. https://doi.org/10.18632/oncotarget.24607

Metrics: PDF 1594 views | HTML 2898 views | ?

Abstract

Sebastian Frees1,2,*, Ines Breuksch3,*, Tobias Haber2, Heide-Katharina Bauer3, Claudia Chavez-Munoz1, Peter Raven1, Igor Moskalev1, Ninadh D´Costa1, Zheng Tan1, Mads Daugaard1, Joachim W. Thüroff2,4, Axel Haferkamp2, Dirk Prawitt5, Alan So1 and Walburgis Brenner2,3

1Department of Urologic Sciences, University of British Columbia, Vancouver Prostate Centre, British Columbia, Canada

2Department of Urology, Johannes Gutenberg University Medical Center, Mainz, Germany

3Department of Gynecology, Johannes Gutenberg University Medical Center, Mainz, Germany

4Current address: Department of Urology, University Clinic Mannheim, Mannheim, Germany

5Department of Pediatrics, Johannes Gutenberg University Medical Center, Mainz, Germany

*These authors contributed equally to this work

Correspondence to:

Sebastian Frees, email: [email protected]

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.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24607

Publication Alerts

Research Papers:

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

Abstract