Zhang Shiwu, Qi Lisha, Li Man, Zhang Danfang, Xu Shaoyan, Wang Ning, Sun Baocun
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, PR China.
J Exp Clin Cancer Res. 2008 Nov 4;27(1):62. doi: 10.1186/1756-9966-27-62.
To identify the roles of CXCL12 and CXCR4 and the associated mechanism involved in perineural invasion of prostate cancer.
The distribution and expression of CXCL12, CXCR4, MMP-2 and MMP-9 in human prostate cancer and in tumor cells invading nerve tissue were studied with immunohistochemical staining. The effects of exogenous CXCL12 and CXCR4 antagonist AMD3100 on PC3 prostate cancer cells invasiveness were assessed in vitro and in vivo.
The expression of CXCL12, CXCR4, MMP-2, and MMP-9 in human prostate cancer were higher than those in hyperplastic prostate tissues (P < 0.05). In vitro CXCL12 could stimulate the PC3 cells invasiveness (P < 0.05) while AMD3100 could inhibit invasiveness. In vivo, the number of nerves around the tumor tissue in the group treated with CXCL12 was significantly higher than that found in the control group (P < 0.05). Both the control group and the CXCL12-treated group had more nerves number near the tumor tissue than it found in the AMD3100-treated group. The positive cell number of CXCL12, CXCR4, MMP-2, MMP-9, and NGF expression ranked from highest to lowest, were the CXCL12-treated, the control, and the AMD3100-treated group(P < 0.05).
CXCL12 and its receptor CXCR4 along with MMP-2 and MMP-9 are related with prostate cancer perineural invasion.
明确趋化因子CXC基元配体12（CXCL12）和CXC趋化因子受体4（CXCR4）的作用以及参与前列腺癌神经周围浸润的相关机制。
采用免疫组化染色法研究CXCL12、CXCR4、基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）在人前列腺癌组织及侵犯神经组织的肿瘤细胞中的分布及表达情况。在体外和体内评估外源性CXCL12和CXCR4拮抗剂AMD3100对PC3前列腺癌细胞侵袭能力的影响。
人前列腺癌组织中CXCL12、CXCR4、MMP-2和MMP-9的表达高于前列腺增生组织（P<0.05）。体外实验中，CXCL12可促进PC3细胞的侵袭能力（P<0.05），而AMD3100可抑制其侵袭能力。在体内，CXCL12处理组肿瘤组织周围的神经数量明显高于对照组（P<0.05）。对照组和CXCL12处理组肿瘤组织附近的神经数量均多于AMD3100处理组。CXCL12、CXCR4、MMP-2、MMP-9和神经生长因子（NGF）表达的阳性细胞数从高到低依次为CXCL12处理组、对照组和AMD3100处理组（P<0.05）。
CXCL12及其受体CXCR4以及MMP-2和MMP-9与前列腺癌神经周围浸润有关。
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