Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses.
Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses.
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DOI：
10.1084/jem.20111627
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发表时间：
2013-07-29
期刊：
影响因子：
--
通讯作者：
Skobe M
中科院分区：
文献类型：
--
作者：
Das S;Sarrou E;Podgrabinska S;Cassella M;Mungamuri SK;Feirt N;Gordon R;Nagi CS;Wang Y;Entenberg D;Condeelis J;Skobe M
阻断CCR8可抑制转移瘤从集合淋巴管进入淋巴结。淋巴管被认为主要通过充当运输系统而促成转移。人们普遍认为，肿瘤细胞通过淋巴液的流动被动地进入淋巴结。我们证明，淋巴结淋巴窦控制肿瘤细胞进入淋巴结，这需要积极的肿瘤细胞迁移。在人类和小鼠组织中，CCL 1蛋白在淋巴结淋巴窦中检测到，但在外周淋巴管中未检测到。CCL1的受体CCR8在人恶性黑色素瘤中强烈表达。通过阻断CCR8或CCL1抑制体外肿瘤细胞向淋巴管内皮细胞（LECs）的迁移，并且重组CCL1促进CCR8+肿瘤细胞的迁移。促炎介质TNF、IL-1 β和LPS增加LEC产生CCL1和肿瘤细胞向LEC迁移。在小鼠模型中，用可溶性拮抗剂阻断CCR8或用shRNA敲低显著降低淋巴结转移。值得注意的是，CCR8的抑制导致肿瘤细胞在与淋巴结被膜下窦交界处的集合淋巴管中的停滞。这些数据鉴定了CCL1-CCR8在转移和淋巴结LEC中作为转移进入淋巴结的关键检查点的新功能。
Blocking CCR8 inhibits entry of metastases from the collecting lymphatic vessel into the lymph node. Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8+ tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibition of CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1–CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes.
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DOI：
10.1084/jem.192.10.1425
发表时间：
2000-11-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gretz JE;Norbury CC;Anderson AO;Proudfoot AE;Shaw S
通讯作者：
Shaw S
影响因子：
4.4
作者：
Gombert, M;Dieu-Nosjean, MC;Homey, B
通讯作者：
Homey, B
影响因子：
2.5
作者：
Düllmann, J;Van Damme, EJM;Schumacher, U
通讯作者：
Schumacher, U
DOI：
10.1084/jem.193.5.573
发表时间：
2001-03-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chensue SW;Lukacs NW;Yang TY;Shang X;Frait KA;Kunkel SL;Kung T;Wiekowski MT;Hedrick JA;Cook DN;Zingoni A;Narula SK;Zlotnik A;Barrat FJ;O'Garra A;Napolitano M;Lira SA
通讯作者：
Lira SA
DOI：
10.1084/jem.20092465
发表时间：
2010-04-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cohen JN;Guidi CJ;Tewalt EF;Qiao H;Rouhani SJ;Ruddell A;Farr AG;Tung KS;Engelhard VH
通讯作者：
Engelhard VH