Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.
Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.
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DOI：
10.18632/oncotarget.22435
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发表时间：
2017-12-05
期刊：
影响因子：
--
通讯作者：
Kadomatsu K
中科院分区：
文献类型：
--
作者：
Su Z;Kishida S;Tsubota S;Sakamoto K;Cao D;Kiyonari S;Ohira M;Kamijo T;Narita A;Xu Y;Takahashi Y;Kadomatsu K
神经聚糖（Neurocan，NCAN）是一种分泌型硫酸软骨素蛋白聚糖，是神经损伤后轴突再生的主要抑制分子之一。然而，它在癌症中的作用尚不清楚。在这里，我们观察到高NCAN表达与神经母细胞瘤（NB）的不良结局密切相关。NCAN也在NB模型TH-MYCN小鼠的早期病变和终末肿瘤中高度和普遍表达。有趣的是，外源性NCAN（即，过表达、重组蛋白和条件培养基）将贴壁NB细胞转化成球体，其在体外（不依赖于锚定的生长和化学抗性）和体内（异种移植物肿瘤生长）的恶性肿瘤被增强。硫酸软骨素的糖链和NCAN的核心蛋白都是球体形成所必需的。CSG 3结构域在NCAN部分中是必需的。我们的综合芯片分析和mRNA表达的RT-qPCR表明，NCAN处理促进细胞分裂，并促使细胞未分化状态。在TH-MYCN小鼠培养的肿瘤球细胞中敲低NCAN导致体外和体内生长抑制。我们的研究结果表明，NCAN，刺激NB细胞，促进恶性表型，是一种细胞外分子提供了癌细胞的生长优势。
Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB). NCAN was also highly and ubiquitously expressed in the early lesions and terminal tumor of TH-MYCN mice, a NB model. Interestingly, exogenous NCAN (i.e., overexpression, recombinant protein and conditioned medium) transformed adherent NB cells into spheres whose malignancies in vitro (anchorage-independent growth and chemoresistance) and in vivo (xenograft tumor growth) were potentiated. Both chondroitin sulfate sugar chains and NCAN's core protein were essential for the sphere formation. The CSG3 domain was essential in the moiety of NCAN. Our comprehensive microarray analysis and RT-qPCR of mRNA expression suggested that NCAN treatment promoted cell division, and urged cells to undifferentiated state. The knockdown of NCAN in tumor sphere cells cultured from TH-MYCN mice resulted in growth suppression in vitro and in vivo. Our findings suggest that NCAN, which stimulates NB cells to promote malignant phenotypes, is an extracellular molecule providing a growth advantage to cancer cells.
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DOI：
10.4161/cc.27983
发表时间：
2014
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Murakami-Tonami Y;Kishida S;Takeuchi I;Katou Y;Maris JM;Ichikawa H;Kondo Y;Sekido Y;Shirahige K;Murakami H;Kadomatsu K
通讯作者：
Kadomatsu K
影响因子：
0.9
作者：
Harigaya, T;Ogawa, H;Nagasawa, H
通讯作者：
Nagasawa, H
影响因子：
4.8
作者：
Milev, P;Chiba, A;Margolis, RU
通讯作者：
Margolis, RU
影响因子：
4.8
作者：
Gaviglio, Angela L.;Knelson, Erik H.;Blobe, Gerard C.
通讯作者：
Blobe, Gerard C.
DOI：
10.1016/j.bbrc.2010.03.085
发表时间：
2010-04-09
影响因子：
3.1
作者：
Asano, Yoshizumi;Kishida, Satoshi;Kadomatsu, Kenji
通讯作者：
Kadomatsu, Kenji