Murine neuronal progenitor cells are preferentially recruited to tumor vasculature via α4-integrin and SDF-1α-dependent mechanisms
Murine neuronal progenitor cells are preferentially recruited to tumor vasculature via α4-integrin and SDF-1α-dependent mechanisms
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DOI：
10.4161/cbt.3.9.1036
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发表时间：
2004-09-01
影响因子：
3.6
通讯作者：
Weissleder, R
中科院分区：
文献类型：
--
作者：
Allport, JR;Patil, VRS;Weissleder, R
最近的研究已经描述了神经元祖细胞在体内向肿瘤募集，然而，介导这种募集的机制还不清楚。当将稳定表达荧光素酶（C17.2-luc）的C17.2鼠神经元祖细胞过继转移到携带皮下刘易斯肺癌的小鼠中时，它们以1%注射剂量/g肿瘤组织积累。在生理相关的流动条件下，C17.2-luc在肿瘤来源的内皮细胞（TEC）上的蓄积和迁移显著高于正常内皮细胞。α（4）-整联蛋白的功能阻断减少了C17.2-luc细胞向正常内皮的募集，但不减少向TEC的募集，然而，SDF-1 α的功能阻断减少了C17.2-luc在TEC上的总体蓄积，并特别减少了跨内皮迁移。总之，这些数据表明，C17.2-luc细胞向TEC的募集是通过SDF-1 α/CXCR 4活化介导的，其导致α（4）-整联蛋白的修饰并导致C17.2-luc细胞募集的改善。
Recent studies have described neuronal progenitor cell recruitment to tumors in vivo, however, the mechanisms mediating this recruitment are not yet understood. When C17.2 murine neuronal progenitors stably expressing luciferase (C17.2-luc) were adoptively transferred into mice carrying subcutaneous Lewis lung carcinomas they accumulated at 1% injected dose/g of tumor tissue. C17.2-luc demonstrated significantly greater accumulation and transmigration on tumor-derived endothelium (TEC) than on normal endothelium under physiologically relevant flow conditions. Function blocking of alpha(4)-integrin reduced recruitment of C17.2-luc cells to normal endothelium but not to TEC, however, function blocking of SDF-1alpha reduced overall accumulation of C17.2-luc on TEC and specifically reduced transendothelial migration. Together, these data suggest that recruitment of C17.2-luc cells to TEC is mediated via SDF-1alpha/CXCR4 activation that results in modification of alpha(4)-integrin and results in improved recruitment of C17.2-luc cells.