| Project/Area Number |
15390489
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Mie University |
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Principal Investigator |
SUGIMURA Yoshiki Mie University, Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, Professor, 大学院医学系研究科, 教授 (90179151)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMA Kiminobu Mie University, Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, Associate Professor, 大学院医学系研究科, 助教授 (10175995)
ONISHI Takehisa Mie University, University Hospital, Nephro-Urologic Surgery and Andrology, Assistant, 医学部附属病院, 助手 (50293783)
SOGA Norihito Mie University, University Hospital, Nephro-Urologic Surgery and Andrology, Assistant, 医学部附属病院, 助手 (60332714)
ISHII Kenichiro Mie University, Graduate School of Medicine, Nephro-Urologic Surgery and Andrology, Assistant, 大学院医学系研究科, 助手 (90397513)
松浦 浩 三重大学, 医学部附属病院, 助手 (60283537)
木瀬 英明 三重大学, 医学部附属病院, 助手 (80293786)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | human prostate cancer / androgen-sensitivity / mesenchymal cells / paracrine signals / epithelial-stromal interaction / tumorigenicity / ヒト前立腺癌 / パラクラインシグナル / 腫瘍形成 / 血管新生 / 前立腺 / 増殖機構 / TGFα / マウス腎皮膜下移植モデル / PSA / ミクロ環境 / 上皮-間質相互作用 / 性ホルモン / 性ホルモン受容体 / 性ホルモン関連遺伝子 / 器官培養 |
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| Research Abstract |
Tumor tissues compose of not only tumor cells but also other components such as stromal cells and blood vessels, which construct tumor microenvironment. Fetal urogenital sinus mesenchyme(UGM) has a characteristic which resembles prostatic cancer-associated fibroblast(CAF). In this study, we investigated the effect of fetal rat UGM(rUGM) which secrets a number of factors as paracrine signals between epithelium and stroma on tumorigenicity of human prostate cancer cells in vivo.
Both of androgen-sensitive LNCaP cells and androgen-insensitive LNCaP subline AIDL cells gave rise to the formation of well-defined globular tumors containing large blood-filled areas at both sub-cutaneous and sub-renal capsule grafting sites. There was no significant difference of gross appearance and histo-pathology between LNCaP and AIDL cells.
Although both LNCaP and AIDL xenografts without fetal rUGM contained large blood-filled areas, recombinants with fetal rUGM reduced those blood-filled areas and increased cancer cell growth. Stromal cells derived from fetal rUGM were observed surrounded cancer cells. Tumor vessel structure in stromal components was. seen as a more uniform appearance of stable vessels. Tumor volume as estimated cancer cell growth with fetal rUGM was calculated. The size of AIDL with fetal rUGM was approximately three times compared with that of LNCaP with fetal rUGM. AR and E-cadherin immunostaining in AIDL with fetal rUGM were decreased apparently.
Our data in experimental prostatic tumor microenvironment have showed that not only paracrine signals from mesenchymal cells but also androgen-sensitivity of cancer cells plays an important role in tumor microenvironment.
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