WISP1/CCN4: a potential target for inhibiting prostate cancer growth and spread to bone.
WISP1/CCN4: a potential target for inhibiting prostate cancer growth and spread to bone.
复制标题
DOI：
10.1371/journal.pone.0071709
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Young MF
中科院分区：
文献类型：
--
作者：
Ono M;Inkson CA;Sonn R;Kilts TM;de Castro LF;Maeda A;Fisher LW;Robey PG;Berendsen AD;Li L;McCartney-Francis N;Brown AC;Crawford NP;Molinolo A;Jain A;Fedarko NS;Young MF
前列腺癌（PC）是男性死亡的主要原因，但调节其进展和最终转移到骨的因素仍不清楚。在这里，我们表明前列腺癌组织中的WISP 1/CCN 4表达在疾病的早期阶段上调，并且进一步表明，它与疾病早期患者血清中WISP 1循环水平的增加相关。在小鼠前列腺癌模型TRAMP中，在晚期癌形成之前发育不全的病变组织中WISP 1也升高。当测试抗WISP 1抗体减少PC 3-Luc细胞向远端部位扩散的能力时，其显示每周两次注射抗WISP 1抗体减少了在小鼠中心内（IC）注射PC 3-Luc细胞后发展的远端肿瘤的数量和总体尺寸。还评估了针对WISP 1的抗体抑制小鼠中PC 3-Luc癌细胞生长的能力，并且显示当在异种移植物中检查时，每周两次注射抗WISP 1抗体减少了局部肿瘤生长。为了更好地理解作用机制，PC 3-Luc细胞通过具有或不具有Matrigel™屏障的膜的迁移显示细胞被吸引至WISP 1，并且这种吸引被用抗WISP 1抗体处理抑制。我们还显示了WISP 1在骨-肿瘤界面和早期癌症基质中的表达，表明WISP 1表达在促进癌症生长及其向骨的扩散中发挥作用。总之，WISP 1在癌症发展的早期阶段的上调，加上其抑制前列腺癌细胞扩散和生长的能力，使其成为前列腺癌的潜在靶点和可获得的诊断标志物。
Prostate cancer (PC) is a leading cause of death in men however the factors that regulate its progression and eventual metastasis to bone remain unclear. Here we show that WISP1/CCN4 expression in prostate cancer tissues was up-regulated in early stages of the disease and, further, that it correlated with increased circulating levels of WISP1 in the sera of patients at early stages of the disease. WISP1 was also elevated in the mouse prostate cancer model TRAMP in the hypoplastic diseased tissue that develops prior to advanced carcinoma formation. When the ability of anti-WISP1 antibodies to reduce the spread of PC3-Luc cells to distant sites was tested it showed that twice weekly injections of anti-WISP1 antibodies reduced the number and overall size of distant tumors developed after intracardiac (IC) injection of PC3-Luc cells in mice. The ability of antibodies against WISP1 to inhibit growth of PC3-Luc cancer cells in mice was also evaluated and showed that twice weekly injections of anti-WISP1 antibodies reduced local tumor growth when examined in xenografts. To better understand the mechanism of action, the migration of PC3-Luc cells through membranes with or without a Matrigel™ barrier showed the cells were attracted to WISP1, and that this attraction was inhibited by treatment with anti-WISP1 antibodies. We also show the expression of WISP1 at the bone-tumor interface and in the stroma of early grade cancers suggested WISP1 expression is well placed to play roles in both fostering growth of the cancer and its spread to bone. In summary, the up-regulation of WISP1 in the early stages of cancer development coupled with its ability to inhibit spread and growth of prostate cancer cells makes it both a potential target and an accessible diagnostic marker for prostate cancer.
登录
查看更多内容
影响因子：
2.7
作者：
Kleer, Celina G.;Zhang, Yanhong;Merajver, Sofia D.
通讯作者：
Merajver, Sofia D.
影响因子：
15.3
作者：
Hashimoto, Y;Shindo-Okada, N;Tani, M;Nagamachi, Y;Takeuchi, K;Shiroishi, T;Toma, H;Yokota, J
通讯作者：
Yokota, J
影响因子：
4
作者：
Inkson, Colette A.;Ono, Mitsuaki;Kuznetsov, Sergei A.;Fisher, Larry W.;Robey, Pamela Gehron;Young, Marian F.
通讯作者：
Young, Marian F.
影响因子：
1.4
作者：
Barqawi AB;Krughoff KJ;Eid K
通讯作者：
Eid K
影响因子：
158.5
作者：
Barry, MJ
通讯作者：
Barry, MJ