2012 Fiscal Year Final Research Report
Exploration for a novel biomarker and a new therapeutic target of castration resistant prostate cancer in terms of cancer microenvironment
| Project/Area Number |
23659755
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
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| Research Institution | Kyoto University |
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Principal Investigator |
SHIMIZU Yousuke 京都大学, 医学研究科, 泌尿器科助教 (00542094)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Takahiro 京都大学, 医学研究科, 助教 (80511881)
OGAWA Osamu 京都大学, 医学研究科, 教授 (90260611)
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| Co-Investigator(Renkei-kenkyūsha) |
NISHI Eiichirou 京都大学, 医学研究科, 准教授
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| Project Period (FY) |
2011 – 2012
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| Keywords | NRDc / バイオマーカー / 前立腺癌 / 去勢抵抗性 |
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| Research Abstract |
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.
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Research Products
(7 results)
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[Journal Article] Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-α.2012
Author(s)
Kanda K, Komekado H, Sawabu T, Ishizu S, Nakanishi Y, Nakatsuji M, Akitake-Kawano R, Ohno M, Hiraoka Y, Kawada M, Kawada K, Sakai Y, Matsumoto K, Kunichika M, Kimura T, Seno H, Nishi E, Chiba T.
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Journal Title
EMBO Mol Med
Volume: 4(5)
Pages: 396-411
DOI
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[Journal Article] Identification and characterization of nardilysin as a novel dimethyl H3K4-binding protein involved in transcriptional regulation.2012
Author(s)
Li J, Chu M, Wang S, Chan D, Qi S, Wu M, Zhou Z, Li J, Nishi E, Qin J, Wong J.
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Journal Title
J Biol Chem
Volume: 287(13)
Pages: 10089-98
DOI
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[Journal Article] SPA-1 controls the invasion and metastasis of human prostate cancer2011
Author(s)
Shimizu Y, Hamazaki Y, Hattori M, Doi K, Terada N, Kobayashi T, Toda Y, Yamasaki T, Inoue TA, Kajita Y, Maeno A, Kamba T, Mikami Y, Kamoto T, Yamada T, Kanno T, Yoshikawa K, Ogawa O, Minato N, Nakamura E
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Journal Title
Cancer Sci
Volume: 102
Pages: 828-36
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