DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.
DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.
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DOI：
10.1016/j.tranon.2018.04.013
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发表时间：
2018-08
影响因子：
5
通讯作者：
Clines GA
中科院分区：
文献类型：
--
作者：
Clines KL;Clines GA
骨转移是晚期乳腺癌和前列腺癌的并发症。肿瘤分泌的Dickkopf同源物1（DKK 1）是经典Wnt信号传导和成骨细胞分化的抑制剂，被提出调节成骨细胞对骨转移癌的反应。本研究的目的是比较乳腺癌和前列腺癌细胞系中DKK 1表达与体内成骨细胞反应，并发现调节癌症DKK 1表达的机制。在骨转移动物模型中，DKK 1在产生溶骨性病变的MDA-MB-231和PC 3细胞中表达最高，因此成骨细胞反应受到抑制。LnCaP、C4-2B、LuCaP23.1、T47 D、ZR-75-1、MCF-7、ARCaP和ARCaPM癌细胞产生成骨细胞、混合或无骨病变，DKK 1表达最低。具有可忽略表达的细胞系LnCaP、C4-2B和T47 D表现出DKK 1启动子的甲基化。然后确定典型Wnt信号传导活性，并在所有测试的细胞系中发现，即使在MDA-MB-231和PC 3细胞系中也是如此，尽管预期相当大量的DKK 1蛋白表达会阻断典型Wnt信号传导。研究了溶骨性细胞系中DKK 1抗性的机制，并确定至少部分是由于MDA-MB-231和PC 3细胞系中DKK 1受体Kremen 1和Kremen 2的下调。DKK 1和Kremen在癌细胞中的联合表达可作为乳腺癌和前列腺癌骨转移成骨细胞反应的预测标志物。
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis. LnCaP, C4-2B, LuCaP23.1, T47D, ZR-75-1, MCF-7, ARCaP and ARCaPM cancer cells that generate osteoblastic, mixed or no bone lesions had the lowest DKK1 expression. The cell lines with negligible expression, LnCaP, C4-2B and T47D, exhibited methylation of the DKK1 promoter. Canonical Wnt signaling activity was then determined and found in all cell lines tested, even in the MDA-MB-231 and PC3 cell lines despite sizeable amounts of DKK1 protein expression expected to block canonical Wnt signaling. A mechanism of DKK1 resistance in the osteolytic cell lines was investigated and determined to be at least partially due to down-regulation of the DKK1 receptors Kremen1 and Kremen2 in the MDA-MB-231 and PC3 cell lines. Combined DKK1 and Kremen expression in cancer cells may serve as predictive markers of the osteoblastic response of breast and prostate cancer bone metastasis.
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影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
2.8
作者：
Hall, Christopher L.;Daignault, Stephanie D.;Shah, Rajal B.;Pienta, Kenneth J.;Keller, Evan T.
通讯作者：
Keller, Evan T.
影响因子：
3.6
作者：
Drake, Justin M.;Danke, Joshua R.;Henry, Michael D.
通讯作者：
Henry, Michael D.
影响因子：
7
作者：
Kim, Jung H.;Dhanasekaran, Saravana M.;Chinnaiyan, Arul M.
通讯作者：
Chinnaiyan, Arul M.
DOI：
10.1111/j.1749-6632.2011.06196.x
发表时间：
2011-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE I
影响因子：
--
作者：
Brunetti, Giacomina;Oranger, Angela;Colucci, Silvia
通讯作者：
Colucci, Silvia