Chemokine receptor CXCR4 expression in patients with melanoma and colorectal cancer liver metastases and the association with disease outcome
Chemokine receptor CXCR4 expression in patients with melanoma and colorectal cancer liver metastases and the association with disease outcome
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DOI：
10.1097/01.sla.0000217690.65909.9c
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发表时间：
2006-07-01
影响因子：
9
通讯作者：
Hoon, Dave S. B.
中科院分区：
文献类型：
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作者：
Kim, Joseph;Mori, Takuji;Hoon, Dave S. B.
目标：为了确定趋化因子受体（CR）的表达在黑色素瘤和结直肠癌（CRC）肝transferation.Summary背景资料：小鼠和体外模型的患者中的作用已确定CR作为潜在的因素，在器官特异性转移的多种癌症。趋化因子通过其各自的受体已被证明，以促进细胞迁移到遥远的organs.Methods：谁接受了黑色素瘤或CRC肝转移肝手术的患者进行了评估。分析黑色素瘤/CRC细胞系和肿瘤标本的筛选cDNA微阵列以鉴定CR。在石蜡包埋的肝转移瘤中，通过定量实时RT-PCR（qRT）验证微阵列数据。迁移试验和免疫组化进行验证CR功能和确认CR expression，respectively.Results：微阵列分析确定CXCR 4作为最常见的CR表达的两种癌症。qRT显示27例黑素瘤中的24例（89%）和29例CRC肝转移中的28例（97%）中有CXCR 4表达。用CXCR 4的配体CXCL 12体外处理黑素瘤或CRC细胞显著增加细胞迁移（P < 0.001）。CRC肝转移灶中CXCR 4低表达与高表达与总生存期的显著差异相关（中位数分别为27个月与10个月; P = 0.036）。在黑色素瘤中，低与高CXCR 4表达的肝转移显示总生存期没有差异（中位数分别为11个月与8个月; P =不显著）。CXCR 4的配体在肝脏中高度表达，可特异性吸引黑色素瘤和CRC CXCR 4（+）细胞。CXCR 4基因表达的定量分析对肝转移患者的预后有重要意义。
Objective: To determine the role of chemokine receptor (CR) expression in patients with melanoma and colorectal cancer (CRC) liver metastases.Summary Background Data: Murine and in vitro models have identified CR as potential factors in organ-specific metastasis of multiple cancers. Chemokines via their respective receptors have been shown to promote cell migration to distant organs.Methods: Patients who underwent hepatic surgery for melanoma or CRC liver metastases were assessed. Screening cDNA microarrays of melanoma/CRC cell lines and tumor specimens were analyzed to identify CR. Microarray data were validated by quantitative real-time RT-PCR (qRT) in paraffin-embedded liver metastases. Migration assays and immunohistochemistry were performed to verify CR function and confirm CR expression, respectively.Results: Microarray analysis identified CXCR4 as the most common CR expressed by both cancers. qRT demonstrated CXCR4 expression in 24 of 27 (89%) melanoma and 28 of 29 (97%) CRC liver metastases. In vitro treatment of melanoma or CRC cells with CXCL12, the ligand for CXCR4, significantly increased cell migration (P < 0.001). Low versus high CXCR4 expression in CRC liver metastases correlated with a significant difference in overall survival (median 27 months vs. 10 months, respectively; P = 0.036). In melanoma, low versus high CXCR4 expression in liver metastases demonstrated no difference in overall survival (median 11 months vs. 8 months, respectively; P = not significant).Conclusions: CXCR4 is expressed and functional on melanoma and CRC cells. The ligand for CXCR4 is highly expressed in liver and may specifically attract melanoma and CRC CXCR4 (+) cells. Quantitative analysis of CXCR4 gene expression in patients with liver metastases has prognostic significance for disease outcome.