Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes
Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes
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DOI：
10.1038/sj.onc.1210267
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发表时间：
2007-07-12
期刊：
影响因子：
8
通讯作者：
Taketo, M. M.
中科院分区：
文献类型：
--
作者：
Kawada, K.;Hosogi, H.;Taketo, M. M.
趋化因子及其受体是白细胞运输的必要条件，也与癌症转移到特定器官有关。我们最近证明了CXCR3在小鼠黑色素瘤细胞转移到淋巴结中起关键作用。在这里，我们发现一些人类结肠癌细胞系组成性地表达CXCR3。我们构建了表达CXCR3 cDNA的细胞（' DLD-1-CXCR3'），并通过裸鼠直肠移植与不表达的对照进行了比较。尽管两种细胞系在2周时以相似的频率播散到淋巴结，但在4周时，DLD-1-CXCR3的扩张速度比对照组快。6周后，59%接种DLD1-CXCR3的小鼠在主动脉旁淋巴结出现宏观转移，而对照组仅为14% （P < 0.05）。相比之下，转移到肝脏或肺是罕见的，不受CXCR3表达的影响。在临床结肠癌样本中，我们发现34%的病例表达CXCR3，其中大部分有淋巴结转移。重要的是，CXCR3阳性癌症患者的预后明显差于未表达CXCR3或表达CXCR4或CCR7的患者。这些结果表明，CXCR3及其配体的激活刺激结肠癌转移优先向预后较差的引流淋巴结转移。
Chemokines and their receptors are essential for leukocyte trafficking, and also implicated in cancer metastasis to specific organs. We have recently demonstrated that CXCR3 plays a critical role in metastasis of mouse melanoma cells to lymph nodes. Here, we show that some human colon cancer cell lines express CXCR3 constitutively. We constructed cells that expressed CXCR3 cDNA (`DLD-1-CXCR3'), and compared with nonexpressing controls by rectal transplantation in nude mice. Although both cell lines disseminated to lymph nodes at similar frequencies at 2 weeks, DLD-1-CXCR3 expanded more rapidly than the control in 4 weeks. In 6 weeks, 59% of mice inoculated with DLD1-CXCR3 showed macroscopic metastasis in para-aortic lymph nodes, whereas only 14% of those with the control (P < 0.05). In contrast, metastasis to the liver or lung was rare, and unaffected by CXCR3 expression. In clinical colon cancer samples, we found expression of CXCR3 in 34% cases, most of which had lymph node metastasis. Importantly, patients with CXCR3-positive cancer showed significantly poorer prognosis than those without CXCR3, or those expressing CXCR4 or CCR7. These results indicate that activation of CXCR3 with its ligands stimulates colon cancer metastasis preferentially to the draining lymph nodes with poorer prognosis.