Factoris promoting local extension of prostate cancer

为了确定导致前列腺癌局部扩散的因素，我们将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，建立原位和睾丸内模型。采用RT-PCR方法分析异种移植物及其转移瘤材料中血管生成相关基因和转移相关基因的信使RNA表达。LNCaP细胞的睾丸内模型显示出更高的肿瘤形成和淋巴结转移发生率，而PC-3细胞在两种模型中都具有高度的致瘤性和转移性。雄激素可增强LNCaP细胞血管生成相关基因mRNA的表达，而PC-3细胞则无此作用。在体内实验中，PC-3细胞比LNCaP细胞表达更高的转移相关基因，包括uPA系统、MMPs和VEGF-C。然后，研究了神经营养因子在几种前列腺癌细胞系（LNCaP、PC-3、DU145、TSUPR）中的表达。4条细胞系均表达NGF， bFGF在PC-3、DU145和TSUPR中表达，nt3在PC-3和DU145中表达。在原位模型中，只有DU145对神经丛的侵袭，提示这些因子的表达与神经丛的侵袭有关。因此，原位/睾丸内前列腺癌细胞模型似乎适合研究肿瘤局部扩展和转移的机制。在临床环境中，证实了前列腺癌细胞浸润到神经周围间隙的NGF表达。然而，VEGF-C的表达与淋巴结转移没有关联。动物模型与临床环境之间的不一致有待进一步研究。

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.