Cadherin-11 in renal cell carcinoma bone metastasis.
Cadherin-11 in renal cell carcinoma bone metastasis.
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Cadherin-11 在肾细胞癌骨转移中的作用
DOI：
10.1371/journal.pone.0089880
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lin SH
中科院分区：
文献类型：
--
作者：
Satcher RL;Pan T;Cheng CJ;Lee YC;Lin SC;Yu G;Li X;Hoang AG;Tamboli P;Jonasch E;Gallick GE;Lin SH
骨是肾细胞癌(RCC)常见的转移部位之一，然而，RCC优先转移到骨的机制尚不清楚。RCC细胞在骨上的归巢/滞留和随后的增殖是RCC细胞在骨中定植的必要步骤。为了探索这些过程发生的可能机制，我们使用了体内转移模型，在该模型中，786-O肾癌细胞被注入SCID小鼠体内，并选择了来自骨、肝脏和淋巴结的有机亲和细胞系。然后在这些选定的细胞中检测影响细胞黏附、血管生成和骨溶解的分子的表达。骨转移786-O细胞(Bo-786-O)是一种主要表达于成骨细胞的间充质钙粘附素，与亲代细胞、肝细胞和淋巴结细胞相比，其细胞表面钙粘蛋白-11的表达显著增加。相反，归巢受体CXCR4在来自所有器官的细胞中同等表达。血管生成因子α、血管生成素1、Tie2、c-Met和溶骨因子PTHrP、IL-6、RANKL的表达差异无统计学意义。亲本细胞和Bo-786-O细胞具有相似的增殖率，而Bo-786-O细胞的迁移能力高于亲本786-O细胞。在Bo-786-O细胞中，使用shRNA敲除钙粘附素-11可以降低迁移速度，这表明在骨源性细胞中观察到的迁移增加与钙粘附素-11有关。人肾癌组织芯片中钙粘蛋白-11表达的免疫组织化学分析表明，在转移到骨的肿瘤中，钙粘蛋白-11阳性的标本数量明显多于原发肿瘤。综上所述，这些结果提示钙粘附素-11可能在肾细胞癌的骨转移中起作用。
Bone is one of the common sites of metastases from renal cell carcinoma (RCC), however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O) compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1α, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis.
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影响因子：
7.3
作者：
Lee, Yu-Chen;Cheng, Chien-Jui;Huang, Miao;Bilen, Mehmet A.;Ye, Xiangcang;Navone, Nora M.;Chu, Khoi;Kao, Hsin-Hsin;Yu-Lee, Li-Yuan;Wang, Zhengxin;Lin, Sue-Hwa
通讯作者：
Lin, Sue-Hwa
影响因子：
6.2
作者：
Käkönen, SM;Mundy, GR
通讯作者：
Mundy, GR
DOI：
10.1073/pnas.1019437108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Chang, Sook Kyung;Noss, Erika H.;Brenner, Michael B.
通讯作者：
Brenner, Michael B.
影响因子：
64.8
作者：
Müller, A;Homey, B;Zlotnik, A
通讯作者：
Zlotnik, A
影响因子：
6.2
作者：
Cheng, SL;Lecanda, F;Civitelli, R
通讯作者：
Civitelli, R