Takeuchi Hiroya, Fujimoto Akihide, Tanaka Maki, Yamano Tomoki, Hsueh Eddy, Hoon Dave S B
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Clin Cancer Res. 2004 Apr 1;10(7):2351-8. doi: 10.1158/1078-0432.ccr-03-0195.
The chemokine CC-ligand 21/secondary lymphoid tissue chemokine (CCL21/SLC) regulates the homing of naïve 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.
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.
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.
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.
趋化因子CC配体21/次级淋巴组织趋化因子（CCL21/SLC）可调节表达CC趋化因子受体7（CCR7）的幼稚T细胞和树突状细胞从远处部位归巢至淋巴结等淋巴组织。我们推测CCL21/SLC可调节携带CCR7的黑色素瘤细胞从原发性病灶迁移至区域肿瘤引流淋巴结。
采用定量实时逆转录聚合酶链反应（qRT）分析和免疫组织化学（IHC）方法评估黑色素瘤细胞系以及原发性和转移性黑色素瘤肿瘤中CCR7的表达水平。在CCL21/SLC诱导下，使用黑色素瘤细胞系进行细胞迁移分析。通过qRT分析和IHC评估肿瘤引流前哨淋巴结（SLN）中CCL21/SLC的表达水平。
通过qRT分析，黑色素瘤细胞系和肿瘤显示出CCR7 mRNA的异质性表达。CCR7 mRNA表达与CCL21/SLC诱导的细胞迁移之间存在很强的功能相关性。原发性黑色素瘤中CCR7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，结果显示，病理检查黑色素瘤阴性的SLN中CCL21/SLC mRNA表达水平显著高于黑色素瘤阳性的SLN（P = 0.008）。
本报告证明了CCR7(+)转移性黑色素瘤细胞募集并归巢至表达CCL21/SLC的肿瘤引流淋巴结的潜在机制。该研究还表明，有转移的淋巴结可能会抑制CCL21/SLC的产生。
