Schindler Adam J, Watanabe Arisa, Howell Stephen B
Moores Cancer Center, University of California, San Diego, CA, USA.
Oncotarget. 2017 Aug 11;9(1):1346-1355. doi: 10.18632/oncotarget.20178. eCollection 2018 Jan 2.
Wnt signaling plays a fundamental role in patterning of the embryo and maintenance of stem cells in numerous epithelia. Epithelial stem cells are closeted in niches created by surrounding differentiated cells that express secreted Wnt and R-spondin proteins that influence proliferation rate and fate determination of stem cell daughters. R-spondins act through the LGR receptors to enhance Wnt signaling. This close association of stem cells with more differentiated regulatory cells expressing Wnt-pathway ligands is a feature replicated in all of the epithelial stem cell systems thus far examined. How the stem cell niche operates through these short-range interactions is best understood for the crypts of the gastrointestinal epithelium and skin. Less well understood are the stem cells that function in the ovarian surface epithelium (OSE) and fallopian tube epithelium (FTE). While the cuboidal OSE appears to be made up of a single cell type, the cells of the FTE progress through a life cycle that involves differentiation into ciliated and secretory subtypes that are eventually shed into the lumen in a manner similar to the gastrointestinal epithelium. Available evidence suggests that high grade serous ovarian carcinoma (HGSOC) originates most often from stem cells in the FTE and that Wnt signaling augmented by LGR6 supports tumor development and progression. This review summarizes current information on LGR5 and LGR6 in the OSE and FTE and how their niches are organized relative to that of the gastrointestinal epithelium and skin.
Wnt信号通路在胚胎模式形成以及众多上皮组织中干细胞的维持方面发挥着基础性作用。上皮干细胞被封闭在由周围分化细胞形成的微环境中，这些分化细胞表达分泌型Wnt和R-spondin蛋白，它们会影响干细胞子代的增殖速率和命运决定。R-spondin通过LGR受体发挥作用以增强Wnt信号通路。干细胞与表达Wnt信号通路配体的更多分化调控细胞之间的这种紧密联系是迄今为止所研究的所有上皮干细胞系统中都存在的一个特征。对于胃肠道上皮和皮肤的隐窝，我们对干细胞微环境如何通过这些短程相互作用发挥作用了解得最为透彻。而对于在卵巢表面上皮（OSE）和输卵管上皮（FTE）中发挥作用的干细胞，我们了解得较少。虽然立方形的OSE似乎由单一细胞类型组成，但FTE的细胞会经历一个生命周期，其中涉及分化为纤毛和分泌亚型，最终以类似于胃肠道上皮的方式脱落到管腔中。现有证据表明，高级别浆液性卵巢癌（HGSOC）最常起源于FTE中的干细胞，并且由LGR6增强的Wnt信号通路支持肿瘤的发生和发展。本综述总结了OSE和FTE中LGR5和LGR6的当前信息，以及它们的微环境相对于胃肠道上皮和皮肤的微环境是如何组织的。
