2001 Fiscal Year Final Research Report Summary
Factoris promoting local extension of prostate cancer
| Project/Area Number |
12671523
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kanazawa University |
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Principal Investigator |
KOSHIDA Kiyoshi Kanazawa Univ. Urology Assoc. Prof., 大学院・医学系研究科, 助教授 (70186667)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA kunihiko Kanazawa Univ. Biotracer Med. Assoc. Prof., 医学部附属病院, 講師 (60230661)
YOKOYAMA osamu Kanazawa Univ. Urology Assist. Prof., 医学部附属病院, 講師 (90242552)
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| Project Period (FY) |
2000 – 2001
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| Keywords | PROSTATE CANCER / LYMPH NODE METASTASIS / PERINEURAL INVASION |
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| Research Abstract |
In order to determine the factors responsible for local extension of prpstate cancer, orthotopic and intratesticular models, were created by injection of LNCaP cells or PC-3 cells into the prostate or testis of severe combined immunodeficient (SCID) mice. Messenger RNA expression ofangiogenesis-related and metastasis-related genes was analyzed by RT-PCR in materials obtained from xenografts and their metastases. The intratesticular model of LNCaP cells showed a higher incidence of tumor formation and lymph node metastasis, while PC-3 cells were highly tu'morigenic and metastastic in both models. Androgen enhanced the in vitro mRNA expression of angiogenesis-related genes in LNCaP cells, but not in PC-3 cells. Higherexpression of metastasis-related genes, including uPA system, MMPs, and VEGF-C in PC-3 cells than LNCaP cells were demonstrated in vivo. Then, expression of neurotrophic factors in several prostate cancercell lines (LNCaP, PC-3, DU145, TSUPR) was investigated.NGF was expressed in all fourlines, while bFGF in PC-3, DU145 and TSUPR, and NT3in PC-3 and DU145. Only DU145 created invasion to neural plexus in orthotopic model, suggesting relationship between the expression of these factors and perineural invasion. Thus, the orthotopic/ intratesticular model wifti prostate cancer cells appears to be suitable for studying the mechanisms of tumor local extension and metastasis. In clinical settings, NGF expression of prostate cancer cells infiltrating into perineural space was demonstrated. However, no con-elation of VEGF-C expression to lymph node metastasis was shown.Discordance between animal models and clinical settings should be further investigated.
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