L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis
L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis
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DOI：
10.1073/pnas.061633698
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发表时间：
2001-03-27
影响因子：
11.1
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Qian, F;Hanahan, D;Weissman, IL
L-选择素介导淋巴细胞归巢至淋巴结（LN）。表达大鼠胰岛素启动子调节的猿猴病毒40标签（RIP-Tag）的转基因小鼠发展转移至肝脏而非LN的大的局部癌症。为了测试这种LN转移的缺乏是否反映它们不存在于循环中，产生表达Tag（T）、L-选择素（L）和大肠杆菌LacZ（Z）的转基因小鼠，在胰腺β细胞中。LTZ小鼠发生胰岛素瘤，特异性地具有LN转移;转移被抗L-选择素mAb阻断，来自这些LN的LacZ（+）肿瘤细胞在转移后归巢到继发性LN。这些结果表明，高度血管化的胰岛癌正在将肿瘤细胞脱落到血流中，这是发生转移的必要但不充分的条件; L-选择素可以促进这些肿瘤细胞归巢到LM，导致转移。
L-selectin mediates homing of lymphocytes to lymph nodes (LN), Transgenic mice that express rat insulin promoter regulated simian virus 40 Tag (RIP-Tag) develop large, local cancers that metastasize to liver but not LN, To test whether this lack of LN metastases reflects their absence from the circulation, transgenic mice were produced that express Tag (T), L-selectin (L), and Escherichia coli LacZ (Z), in pancreatic beta cells. LTZ mice developed insulinomas that specifically had LN metastases; metastasis was blocked by an anti L-selectin mAb, LacZ(+) tumor cells from these LN homed to secondary LN upon transfer. These results suggest that the highly vascularized islet carcinomas are shedding tumor cells into the bloodstream, which is a necessary but insufficient condition for metastasis to occur; L-selectin can facilitate homing of such tumor cells to LM, resulting in metastasis.