Qian F, Hanahan D, Weissman I L
Department of Pathology and Developmental Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3976-81. doi: 10.1073/pnas.061633698. Epub 2001 Mar 13.
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 LN, resulting in metastasis.
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控的猿猴病毒40大T抗原（RIP-Tag）的转基因小鼠会发生大型局部癌症，这些癌症会转移至肝脏，但不会转移至淋巴结。为了测试这种淋巴结转移的缺失是否反映了肿瘤细胞在循环系统中的缺失，研究人员培育了在胰腺β细胞中表达大T抗原（T）、L-选择素（L）和大肠杆菌LacZ（Z）的转基因小鼠。LTZ小鼠发生了胰岛素瘤，且这些胰岛素瘤会特异性地发生淋巴结转移；抗L-选择素单克隆抗体可阻断转移。这些淋巴结中的LacZ（+）肿瘤细胞在转移后会归巢至二级淋巴结。这些结果表明，高度血管化的胰岛癌会将肿瘤细胞释放到血液中，这是发生转移的必要但不充分条件；L-选择素可促进此类肿瘤细胞归巢至淋巴结，从而导致转移。
