Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.
Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.
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上皮性卵巢癌（EOC）是美国女性癌症死亡的第五大原因，但其发病机制尚不清楚。已知一些上皮癌发生在两种上皮之间的过渡区，而其他上皮癌则起源于上皮组织干细胞。卵巢表面上皮（OSE）的干细胞壁龛在排卵期间破裂并再生，目前尚未明确定义。在这里，我们确定了小鼠卵巢门区，OSE，间皮和输卵管（输卵管）上皮之间的过渡/连接区域是以前未被识别的OSE干细胞生态位。我们发现门部OSE细胞循环缓慢，表达干细胞/祖细胞标志物ALDH1、Lgr5、Lef1、CD133和CK6b。这些细胞在体外和体内显示出长期的干细胞特性，正如我们的系列球体生成和长期谱系追踪分析所显示的那样。重要的是，在肿瘤抑制基因Trp53和Rb1失活后，门细胞表现出更高的转化潜力，这两种基因的途径在最具侵袭性和最常见的人类EOC（高级别浆液性腺癌）中经常发生改变。我们的实验研究支持这样一种观点，即过渡区对恶性转化的易感性可能是由这些区域中干细胞壁龛的存在来解释的。确定OSE的干细胞生态位可能对理解EOC的发病机制具有重要意义。
Epithelial ovarian cancer (EOC) is the fifth-leading cause of cancer death among women in the United States, but its pathogenesis is poorly understood . Some epithelial cancers are known to occur in transitional zones between two types of epithelium, while others have been shown to originate in epithelial tissue stem cells . The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been unequivocally defined. Here we identify the hilum region of the mouse ovary, the transitional/junction area between OSE, mesothelium and tubal (oviductal) epithelium as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are slowly-cycling and express stem/progenitor cell markers ALDH1, Lgr5, Lef1, CD133, and CK6b. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and by long-term lineage tracing assays. Importantly, the hilum cells exhibit increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are frequently altered in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma . Our study experimentally supports the notion that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis.