Exploration for a novel biomarker and a new therapeutic target of castration resistant prostate cancer in terms of cancer microenvironment

从癌症微环境角度探索去势抵抗性前列腺癌新生物标志物和新治疗靶点

• 批准号: 23659755
• 负责人: SHIMIZU Yousuke
• 金额: $ 2.16万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659755/
• 关键词: NRDc; バイオマーカー; 前立腺癌; 去勢抵抗性; 癌微小環境

a)Introduction and ObjectiveProstate specific antigen (PSA) is a diagnostic or therapeutic biomarker for prostate cancer (PC). However, due to its low specificity and lack of relevance with aggressiveness, novel biomarkers to complement PSA are definitely needed. We previously reported that Nardilysin (NRDc) promotes ectodomain shedding of the precursor forms of various growth factors and cytokines, such as heparin-binding epidermal growth factor-like growth factor (HB-EGF) and tumor necrosis factor-α (TNFα) (Nishi et al, 2006). The aim of our study is to evaluate the association of NRDc with PC aggressiveness and its potential to be a prognostic marker.b)Methods NRDc expression levels in LNCaP and PC3 cells were analyzed by real-time PCR and Western blotting. To evaluate the association with cell invasiveness, NRDc was knocked-down in PC3, and in vitro Matrigel invasion assays and in vivo xenograft tumor growth assays were performed in these cells. Then, NRDc expression levels in PC tissues were evaluated by immunohistochemistry (IHC), and NRDc serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from PC patients.c) Results The expression levels of NRDc were higher in PC3 than in LNCaP. NRDc knocking-down suppressed in vitro cell invasion and in vivo cell proliferation. In IHC analysis the NRDc expression levels tended to be positively correlated with biochemical reccurence after surgical treatment (p=0.30). Serum NRDc concentrations in PC patients (652 pg/ml±1950, n=161) were significantly higher than in normal controls (303 pg/ml±510, n=20) (p=0.0269), especially in metastatic PC patients, and tended to be correlated with patients prognosis. The serum NRDc levels were not correlated with serum PSA levels in PC patients.d) Conclusions. NRDc was associated with PC aggressiveness, being potential tissue and serum markers for predicting PC prognosis.

前列腺特异性抗原（PSA）是前列腺癌（PC）的诊断或治疗生物标志物。然而，由于其低特异性和缺乏相关性的侵略性，新的生物标志物，以补充PSA是肯定需要的。我们之前报道了Nardilysin（NRDc）促进各种生长因子和细胞因子前体形式的胞外域脱落，如肝素结合表皮生长因子样生长因子（HB-EGF）和肿瘤坏死因子-α（TNFα）（Nishi et al，2006）。本研究的目的是评估NRDc与PC侵袭性的相关性及其作为预后标志物的潜力。B）方法通过实时PCR和Western印迹分析LNCaP和PC 3细胞中NRDc的表达水平。为了评估与细胞侵袭性的关联，在PC 3中敲低NRDc，并在这些细胞中进行体外基质胶侵袭测定和体内异种移植肿瘤生长测定。结果NRDc在PC 3中的表达水平高于LNCaP。NRDc敲低抑制体外细胞侵袭和体内细胞增殖。在IHC分析中，NRDc表达水平倾向于与手术治疗后的生化复发呈正相关（p=0.30）。PC患者血清NRDc浓度（652 pg/ml±1950，n=161）显著高于正常对照组（303 pg/ml±510，n=20）（p=0.0269），尤其是转移性PC患者，并与患者预后相关。PC患者血清NRDc水平与血清PSA水平无相关性。NRDc与PC的侵袭性相关，是预测PC预后的潜在组织和血清标志物。

项目成果

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with T1C-T2NOMO prostate cancer

三维适形放射治疗联合新辅助激素治疗日本 T1C-T2NOMO 前列腺癌患者的长期结果

• DOI: 10.1007/s10147-011-0326-z
• 发表时间: 2011
• 期刊: Int J Clin Oncol.
• 作者: Mizowaki T;Takayama K;Norihisa Y;Ogura M;Kamba T;Inoue T;Shimizu Y;Kamoto T;Ogawa O;Hiraoka M
• 通讯作者: Hiraoka M

SPA-1 controls the invasion and metastasis of human prostate cancer

• DOI: 10.1111/j.1349-7006.2011.01876.x
• 发表时间: 2011-04-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Shimizu, Yosuke;Hamazaki, Yoko;Nakamura, Eijiro
• 通讯作者: Nakamura, Eijiro

Nardilysinは予後不良前立腺癌診断マーカーとなり得る

纳尔迪溶素可作为预后不良的前列腺癌的诊断标志物

• 发表时间: 2013
• 作者: 後藤崇之;寺田直樹;井上貴博;吉川武志;小林恭;清水洋祐;神波大己;吉村耕治;西英一郎;小川修
• 通讯作者: 小川修

Focal adhesion kinase activity correlates with biochemical recurrence after radical prostatectomy

粘斑激酶活性与根治性前列腺切除术后生化复发相关

• 发表时间: 2011
• 作者: 後藤崇之;寺田直樹;井上貴博;吉川武志;小林恭;清水洋祐;神波大己;吉村耕治;西英一郎;小川修;井上貴博 小林恭 前野淳 赤松秀輔 岡田能幸 吉川武志 清水洋祐 神波大己 小川修
• 通讯作者: 井上貴博 小林恭 前野淳 赤松秀輔 岡田能幸 吉川武志 清水洋祐 神波大己 小川修

京都大学医学研究科泌尿器科学教室HP

京都大学大学院医学研究科泌尿外科 HP