PDF(Pubmed)
Abstract：
Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor evolution. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. Here we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify loss of stromal KITL during tumorigenesis as tumor-promoting. Genetic inhibition of mesenchymal KITL in the contexts of homeostasis, injury, and cancer together indicate a role for KITL signaling in maintenance of pancreas tissue architecture, such that loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment.
摘要：
正常组织结构的组分充当肿瘤进展的屏障。炎症和伤口愈合程序是实体瘤发生的必要特征，其中对免疫和非免疫基质元件的改变使得在肿瘤进化期间内稳态的丧失。正常基质细胞状态限制组织可塑性和肿瘤发生的确切机制，在肿瘤进展过程中丢失，基本上是未知的。在这里，我们显示健康的胰腺间质表达旁分泌信号分子KITL，也被称为干细胞因子，并将肿瘤发生过程中基质KITL的丢失确定为促进肿瘤。在体内平衡的情况下，间充质KITL的遗传抑制，损伤,和癌症共同表明了KITL信号在维持胰腺组织结构中的作用，这样基质KITL池的丢失增加了肿瘤生长并降低了荷瘤小鼠的存活率。一起,这些发现暗示间充质KITL的缺失是建立肿瘤许可微环境的一种机制.
■通过分析健康和肿瘤相关的胰腺间质的转录程序，我们发现健康胰腺组织中的间充质细胞亚群表达旁分泌信号因子KITL。间充质KITL的丢失是胰腺肿瘤演变的一个伴随和允许的特征，对癌症拦截有潜在的影响。
■通过分析健康和肿瘤相关的胰腺间质的转录程序，我们发现健康胰腺组织中的间充质细胞亚群表达旁分泌信号因子KITL。间充质KITL的丢失是胰腺肿瘤演变的一个伴随和允许的特征，对癌症拦截有潜在的影响。
