CCL21 chemokine regulates chemokine receptor CCR7 bearing malignant melanoma cells
CCL21 chemokine regulates chemokine receptor CCR7 bearing malignant melanoma cells
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DOI：
10.1158/1078-0432.ccr-03-0195
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发表时间：
2004-04-01
影响因子：
11.5
通讯作者：
Hoon, DSB
中科院分区：
文献类型：
--
作者：
Takeuchi, H;Fujimoto, A;Hoon, DSB
目的：趋化因子CC-配体21/次级淋巴组织趋化因子（CCL 21/SLC）调节表达CC-趋化因子受体7（CCR 7）的幼稚T细胞和树突状细胞从远端部位归巢至淋巴组织如淋巴结。我们假设，CCL 21/SLC调节迁移的CCR 7轴承黑色素瘤细胞从一个原发性病变的区域肿瘤引流lymph nodes.Experimental设计：定量实时逆转录酶-PCR（qRT）测定和免疫组化（IHC）被用来评估黑色素瘤细胞系和原发性和转移性黑色素瘤中CCR 7的表达水平。在CCL 21/SLC的诱导下，使用黑素瘤细胞系进行细胞迁移测定。结果：qRT法检测黑色素瘤细胞系和肿瘤组织中CCL 21/SLC mRNA的表达均呈异质性。CCL 21/ SLC诱导的细胞迁移与CCR 7 mRNA表达之间存在较强的功能相关性。原发性黑色素瘤中CCR 7表达的IHC证据与Breslow厚度显著相关（P = 0.02）。通过qRT分析对55例黑色素瘤患者的SLN进行评估，结果表明，病理学上黑色素瘤阴性的SLN中CCL 21/SLC mRNA表达水平显著高于黑色素瘤阳性的SLNs.Conclusions（P = 0.008）：本报告证实了CCR 7（+）转移性黑色素瘤细胞募集并归巢至表达CCL 21/SLC的肿瘤引流淋巴结的潜在机制。该研究还表明，携带转移的淋巴结可能抑制CCL 21/SLC的产生。
Purpose: The chemokine CC-ligand 21/secondary lymphoid tissue chemokine (CCL21/SLC) regulates the homing of naive T cells and dendritic cells that express CC-chemokine receptor 7 (CCR7) from distant sites to lymphoid tissue such as lymph nodes. We hypothesized that CCL21/SLC regulates the migration of CCR7-bearing melanoma cells from a primary lesion to regional tumor-draining lymph nodes.Experimental Design: Quantitative real-time reverse transcriptase-PCR (qRT) assay and immunohistochemistry (IHC) were used to assess the level of CCR7 expression in melanoma cell lines and in primary and metastatic melanoma tumors. Cell migration assay using melanoma cell lines was performed under the induction of CCL21/SLC. The CCL21/SLC expression level in tumor-draining sentinel lymph nodes (SLNs) was assessed by both qRT assay and IHC.Results: Melanoma cell lines and tumors demonstrated heterogeneous expression of CCR7 mRNA by qRT assay. There was strong functional correlation between CCR7 mRNA expression and cell migration induced by CCL21/ SLC. IHC evidence of CCR7 expression in primary melanomas significantly (P = 0.02) correlated with Breslow thickness. Assessment of SLN from 55 melanoma patients by qRT assay demonstrated that CCL21/SLC mRNA expression level was significantly (P = 0.008) higher in pathologically melanoma-negative SLNs than in melanoma-positive SLNs.Conclusions: This report demonstrates a potential mechanism for recruitment and homing of CCR7(+) metastatic melanoma cells to tumor-draining lymph nodes, which express CCL21/SLC. The study also suggests that lymph nodes bearing metastasis may suppress CCL21/SLC production.