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钙敏感受体（CaSR）促进肾细胞癌骨转移的发展。

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

作者信息

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

机构信息

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

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

出版信息

Oncotarget. 2018 Mar 2;9(21):15766-15779. doi: 10.18632/oncotarget.24607. eCollection 2018 Mar 20.

DOI:10.18632/oncotarget.24607
PMID:29644008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5884663/
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 and . The RCC cell line 786-O was stably transfected with the 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 -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 -transfected cells. These effects were abolished by NPS2143. Development of bone metastasis was evaluated 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.

摘要

骨转移是肾细胞癌（RCC）的一个重要预后因素。钙敏感受体（CaSR）已在几种不同的恶性肿瘤中与骨转移相关联。我们分析了CaSR在RCC骨转移中的作用。将RCC细胞系786 - O用该基因进行稳定转染，并单独用钙或与CaSR拮抗剂NPS2143联合处理。之后分析迁移、黏附、增殖及显著的信号分子。经钙处理的转染768 - O细胞对内皮细胞以及细胞外基质成分纤连蛋白和I型胶原的黏附增加，但对IV型胶原的黏附未增加。趋化性细胞迁移和增殖也由钙诱导。钙处理转染细胞后，SHC、AKT、ERK、P90RSK和JNK的活性增强。这些作用被NPS2143消除。在小鼠模型中评估骨转移的发生情况。心内注射CaSR转染的768 - O细胞显示骨转移率增加。结果表明CaSR是RCC骨转移机制中的一个重要组成部分。因此，靶向CaSR可能对CaSR高表达的骨转移性RCC患者有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/93a136c8e15d/oncotarget-09-15766-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/4cace65971fb/oncotarget-09-15766-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/4126605feb50/oncotarget-09-15766-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/3f5fb4920c7d/oncotarget-09-15766-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/47880485445a/oncotarget-09-15766-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/eee7b2311589/oncotarget-09-15766-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/e2691fee6ae8/oncotarget-09-15766-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/93a136c8e15d/oncotarget-09-15766-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/4cace65971fb/oncotarget-09-15766-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/4126605feb50/oncotarget-09-15766-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/3f5fb4920c7d/oncotarget-09-15766-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/47880485445a/oncotarget-09-15766-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/eee7b2311589/oncotarget-09-15766-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/e2691fee6ae8/oncotarget-09-15766-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4469/5884663/93a136c8e15d/oncotarget-09-15766-g007.jpg

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