Seno Hiroshi, Yamaga Yuichi, Nakanishi Yuki, Chiba Tsutomu
Nihon Rinsho. 2015 May;73(5):850-4.
Tumor therapies targeting tumor stem cells(TSCs) have been limited. One of the reasons is that TSC markers are often shared by normal stem cells (NSCs), and therapies targeting those marker-positive cells may cause severe injury to normal tissues. To solve the problem, we focused on doublecortin -like kinase 1 (Dclk1). In the normal intestines of Dclk1(creERT2/+); Rosa26(LacZ/+) mice, LacZ-labeled epithelial cells were scattered along villi after tamoxifen injection. In contrast, in Dclk1(creERT2/+); Rosa26(LacZ/+); Apc(Min/+) mice, intestinal tumors were occupied by LacZ-labeled tumor cells, and selective ablation of Dclk1-positive cells using iDTR system resulted in regression of intestinal tumors without apparent damage to the normal intestines. Thus, Dclk1 appeared to be a marker that discriminates TSCs from NSCs in the intestine.
针对肿瘤干细胞（TSCs）的肿瘤治疗一直受到限制。原因之一是TSC标志物常常也存在于正常干细胞（NSCs）中，针对那些标志物阳性细胞的治疗可能会对正常组织造成严重损伤。为了解决这个问题，我们聚焦于双皮质素样激酶1（Dclk1）。在注射他莫昔芬后，Dclk1(creERT2/+); Rosa26(LacZ/+)小鼠的正常肠道中，LacZ标记的上皮细胞沿绒毛呈散在分布。相比之下，在Dclk1(creERT2/+); Rosa26(LacZ/+); Apc(Min/+)小鼠中，肠道肿瘤被LacZ标记的肿瘤细胞占据，并且使用iDTR系统选择性消融Dclk1阳性细胞导致肠道肿瘤消退，而对正常肠道没有明显损伤。因此，Dclk1似乎是一种能在肠道中区分TSCs和NSCs的标志物。
