Factoris promoting local extension of prostate cancer

为了确定前列腺癌局部扩散的相关因素，将LNCaP细胞或PC-3细胞分别注射到重度联合免疫缺陷(SCID)小鼠的前列腺或睾丸内，建立了前列腺癌局部扩散的原位和睾丸模型。RT-PCR分析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信使RNA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细胞模型的成瘤率和转移率均较高。雄激素可促进体外培养的LNCaP细胞血管生成相关基因的mRNA表达，但对PC-3细胞无明显影响。PC-3细胞中uPA系统、MMPs和VEGF-C等转移相关基因的表达水平明显高于LNCaP细胞。神经营养因子在前列腺癌细胞系LNCaP、PC-3、DU145、TSUPR中均有表达，其中NGF在PC-3、DU145和TSUPR中均有表达，bFGF在PC-3、DU145和TSUPR中均有表达，NT3在PC-3和DU145中均有表达。在原位模型中，只有DU145对神经丛有侵袭作用，提示这些因子的表达与神经侵袭有关。因此，前列腺癌原位/睾丸内模型适合于研究肿瘤局部扩散和转移的机制。在临床环境中，前列腺癌细胞在神经周围间隙中有NGF的表达。然而，未发现血管内皮生长因子-C的表达与淋巴结转移有关，动物模型和临床环境之间的不一致性有待进一步研究。

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.