Alwosaibai Kholoud, Abedini Atefeh, Al-Hujaily Ensaf M, Tang Yong, Garson Kenneth, Collins Olga, Vanderhyden Barbara C
Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada.
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ontario, Canada.
Oncotarget. 2017 Aug 10;8(44):76881-76897. doi: 10.18632/oncotarget.20173. eCollection 2017 Sep 29.
Recent studies have provided evidence that the secretory cells of the fallopian tube (oviduct) are a probable origin for high-grade serous ovarian carcinoma. In addition to secretory cells, the fallopian tube epithelium consists of ciliated cells and CD44+ undifferentiated stem-like cells. Loss of PAX2 expression is recognized as an early event in epithelial transformation, but the specific role of PAX2 in this transition is unknown. The aim of this study was to define the role of PAX2 in oviductal epithelial (OVE) cells and its response to transforming growth factor β1 (TGFβ), characterizing specifically its potential involvement in regulating stem cell-like behaviors that may contribute to formation of cancer-initiating cells. Treatment of primary cultures of mouse OVE cells with TGFβ induced an epithelial-mesenchymal transition (EMT) associated with decreased expression of PAX2 and an increase in the fraction of cells expressing CD44. PAX2 knockdown in OVE cells and overexpression in ovarian epithelial cells confirmed that PAX2 inhibits stem cell characteristics and regulates the degree of epithelial differentiation of OVE cells. These results suggest that loss of PAX2, as occurs in serous tubal intraepithelial carcinomas, may shift secretory cells to a more mesenchymal phenotype associated with stem-like features.
最近的研究已提供证据表明，输卵管的分泌细胞可能是高级别浆液性卵巢癌的起源。除了分泌细胞外，输卵管上皮还由纤毛细胞和CD44 +未分化的干细胞样细胞组成。PAX2表达缺失被认为是上皮转化的早期事件，但PAX2在这种转变中的具体作用尚不清楚。本研究的目的是确定PAX2在输卵管上皮（OVE）细胞中的作用及其对转化生长因子β1（TGFβ）的反应，具体表征其在调节可能有助于癌症起始细胞形成的干细胞样行为中的潜在作用。用TGFβ处理小鼠OVE细胞的原代培养物可诱导上皮-间质转化（EMT），这与PAX2表达降低和表达CD44的细胞比例增加有关。OVE细胞中PAX2的敲低和卵巢上皮细胞中PAX2的过表达证实，PAX2抑制干细胞特征并调节OVE细胞的上皮分化程度。这些结果表明，如在输卵管上皮内癌中发生的那样，PAX2的缺失可能会使分泌细胞转变为与干细胞样特征相关的更具间充质的表型。
