Factoris promoting local extension of prostate cancer

促进前列腺癌局部扩散的因素

• 批准号: 12671523
• 负责人: KOSHIDA Kiyoshi
• 金额: $ 2.18万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671523/
• 关键词: PROSTATE CANCER; LYMPH NODE METASTASIS; PERINEURAL INVASION

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.

为了确定导致前列腺癌局部扩散的因素，通过将LNCaP细胞或PC-3细胞注射到严重联合免疫缺陷（SCID）小鼠的前列腺或睾丸中来建立原位和睾丸内模型。采用RT-PCR方法检测移植瘤及其转移瘤组织中血管生成相关基因和转移相关基因的mRNA表达。睾丸内LNCaP细胞模型的成瘤率和淋巴结转移率较高，而PC-3细胞在两种模型中均具有高度致瘤性和淋巴结转移性。雄激素可增强LNCaP细胞中血管生成相关基因的体外mRNA表达，但在PC-3细胞中无此作用。在体内实验中，PC-3细胞中的转移相关基因，包括uPA系统、MMPs和VEGF-C的表达高于LNCaP细胞。然后，我们检测了几种前列腺癌细胞系（LNCaP、PC-3、DU 145、TSUPR）中神经营养因子的表达，结果发现，NGF在四种细胞系中均有表达，bFGF在PC-3、DU 145和TSUPR中均有表达，NT 3在PC-3和DU 145中均有表达。在原位模型中，只有DU 145对神经丛产生侵袭，提示这些因子的表达与神经侵袭有关。因此，原位/睾丸内模型wifti前列腺癌细胞似乎是适合于研究肿瘤局部扩展和转移的机制。在临床环境中，前列腺癌细胞浸润到神经周围空间的NGF表达得到证实。但VEGF-C表达与淋巴结转移无相关性，动物模型与临床的不一致性有待进一步研究。