Rubie Claudia, Frick Vilma Oliveira, Wagner Mathias, Weber Christina, Kruse Bianca, Kempf Katja, König Jochen, Rau Bettina, Schilling Martin
Department of General-, Visceral-, Vascular- and Paediatric Surgery, Universitatsklinikum des Saarlandes, Chirurgische Klinik, Gebaude 57, Homburg/Saar 66421, Germany.
World J Gastroenterol. 2006 Nov 7;12(41):6627-33. doi: 10.3748/wjg.v12.i41.6627.
To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3beta), CCL20 (MIP-3alpha) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases.
Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent non-tumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT-PCR and Western blot analysis in the same cases of HCC and CRLM.
Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues.
Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.
评估并比较肝细胞癌(HCC)与结直肠癌肝转移(CRLM)中趋化因子CXCL12(SDF-1)、CCL19(MIP-3β)、CCL20(MIP-3α)和CCL21(6Ckine,Exodus2)及其受体在RNA和蛋白质水平的表达谱,并阐明它们对恶性肝脏疾病发生发展的影响。
分别采用逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)分析11例HCC标本、23例CRLM标本及其相应的癌旁非肿瘤肝组织中的趋化因子表达情况。采用RT-PCR和蛋白质免疫印迹分析,对相同病例的HCC和CRLM组织中其受体CXCR4、CCR6和CCR7的表达进行分析。
在两种癌症类型中均检测到CCL20/CCR6显著上调。此外,与HCC组织相比,CCL20在CRLM中表现出显著过表达。CXCR4仅在CRLM中显著上调,相对于HCC组织呈现异常表达模式。
CXCR4表达与CRLM的相关性表明CXCR4可能是CRLM的潜在预测因子。HCC和CRLM中CCL20及其受体CCR6的高表达,以及与HCC组织相比CRLM中CCL20显著上调,表明CCL20/CCR6配体-受体对参与了肝脏恶性肿瘤的发生发展。