Involvement of an autocrine stromal cell-derived Factor-1/CXCR4 system on the distant metastasis of human oral squamous cell carcinoma
Involvement of an autocrine stromal cell-derived Factor-1/CXCR4 system on the distant metastasis of human oral squamous cell carcinoma
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DOI：
10.1158/1541-7786.mcr-06-0368
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发表时间：
2007-07-01
影响因子：
5.2
通讯作者：
Sato, Mitsunobu
中科院分区：
文献类型：
--
作者：
Uchida, Daisuke;Noue, Tornitaro;Sato, Mitsunobu
我们之前已经表明，在口腔鳞状细胞癌（SCC）中，基质细胞衍生因子-1 (SDF-1; CXCL12)/CXCR4系统参与淋巴结转移的建立，但不参与远处转移。在本研究中，我们研究了自分泌的SDF-1/CXCR4系统在口腔SCC细胞远处转移中的作用。原发口腔SCCs和转移性淋巴结的SDF-1和CXCR4免疫组化染色显示，转移性淋巴结中SDF-1阳性病例的数量明显高于原发口腔SCCs，这与前者的生存率较低有关。B88细胞表现出功能性CXCR4和淋巴结转移潜能（即自分泌的SDF-1/CXCR4系统），在B88细胞中强制表达SDF-1，赋予细胞增强的细胞运动性和不依赖于电荷的生长潜能。裸鼠原位接种转染物与转移淋巴结数量增加和淋巴结转移灶更具侵袭性有关。此外，SDF-1转染体（即自分泌的SDF-1/CXCR4系统）在移植后表现出明显的肺转移。而模拟转染（即旁分泌SDF-1/CXCR4系统）则没有。在本实验条件下，CXCR4拮抗剂AMD3100可显著抑制SDF-1转染体的肺转移，改善体重减轻，提高荷瘤裸鼠存活率。这些结果表明，在口服SCC病例中，旁分泌的SDF-1/CXCR4系统增强了淋巴结转移，但远处转移可能需要自分泌的SDF-1/CXCR4系统。
We have previously shown that a stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of lymph node metastasis, but not in that of distant metastasis, in oral squamous cell carcinoma (SCC). In this study, we investigated the role of the autocrine SDF-1/CXCR4 system, with a focus on distant metastasis in oral SCC cells. The immunohistochemical staining of SDF-1 and CXCR4 using primary oral SCCs and metastatic lymph nodes showed a significantly higher number of SDF-1-positive cases among the metastatic lymph nodes than among the primary oral SCCs, which was associated with a poor survival rate among those of the former group. The forced expression of SDF-1 in B88 cells, which exhibit functional CXCR4 and lymph node metastatic potential (i.e., the autocrine SDF-1/CXCR4 system), conferred enhanced cell motility and an chorage-independent growth potential onto the cells. Orthotopic inoculation of the transfectant into nude mice was associated with an increase in the number of metastatic lymph nodes and more aggressive metastatic foci in the lymph nodes. Furthermore, the SDF-1 transfectant (i.e., the autocrine SDF-1/CXCR4 system) exhibited dramatic metastasis to the lung after im. inoculation, whereas the mock transfectant (i.e., the paracrine SDF-1/CXCR4 system) did not. Under the present conditions, AMD3100, a CXCR4 antagonist, significantly inhibited the lung metastasis of the SDF-1 transfectant, ameliorated body weight loss, and improved the survival rate of tumor-bearing nude mice. These results suggested that, in cases of oral SCC, the paracrine SDF-1/CXCR4 system potentiates lymph node metastasis, but distant metastasis might require the autocrine SDF-1/CXCR4 system.