...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of clinical investigation >Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations
【24h】

Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations

机译：小鼠基底细胞癌源自毛囊干细胞和多个上皮祖细胞群

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Uncontrolled Hedgehog (Hh) signaling leads to the development of basal cell carcinoma (BCC), the most common human cancer, but the cell of origin for BCC is unclear. While Hh pathway dysregulation is common to essentially all BCCs, there exist multiple histological subtypes, including superficial and nodular variants, raising the possibility that morphologically distinct BCCs may arise from different cellular compartments in skin. Here we have shown that induction of a major mediator of Hh signaling, GLI2 activator (GLI2ΔN), selectively in stem cells of resting hair follicles in mice, induced nodular BCC development from a small subset of cells in the lower bulge and secondary hair germ compartments. Tumorigenesis was markedly accelerated when GLI2ΔN was induced in growing hair follicles. In contrast, induction of GLI2ΔN in epidermis led to the formation of superficial BCCs. Expression of GLI2ΔN at reduced levels in mice yielded lesions resembling basaloid follicular hamartomas, which have previously been linked to low-level Hh signaling in both mice and humans. Our data show that the cell of origin, tissue context (quiescent versus growing hair follicles), and level of oncogenic signaling can determine the phenotype of Hh/Gli-driven skin tumors, with high-level signaling required for development of superficial BCC-like tumors from interfollicular epidermis and nodular BCC-like tumors from hair follicle stem cells.
机译：不受控制的刺猬（Hh）信号传导导致基底细胞癌（BCC）的发展，基底细胞癌是最常见的人类癌症，但BCC的起源细胞尚不清楚。虽然Hh通路失调基本上是所有BCC所共有的，但存在多种组织学亚型，包括浅表和结节变体，从而增加了形态学上不同的BCC可能来自皮肤中不同的细胞区室的可能性。在这里，我们已经表明，Hh信号的主要介体GLI2激活剂（GLI2ΔN）的诱导选择性地在小鼠静息毛囊的干细胞中诱导了从下膨出和次生发芽室中的一小部分细胞形成结节性BCC的发展。在生长的毛囊中诱导GLI2ΔN时，肿瘤发生明显加快。相反，表皮中GLI2ΔN的诱导导致浅表BCC的形成。在小鼠中以降低的水平表达GLI2ΔN产生类似于基底样卵泡错构瘤的损伤，其先前已与小鼠和人类中的低水平Hh信号传导相关。我们的数据表明，起源细胞，组织背景（静止的毛囊与正在生长的毛囊）以及致癌信号的水平可以确定Hh / Gli驱动的皮肤肿瘤的表型，而浅表BCC样细胞的发育则需要高水平的信号卵泡间表皮肿瘤和毛囊干细胞样结节性BCC样肿瘤。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号