Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Cell Death Dis. 2021 Apr 7;12(4):375. doi: 10.1038/s41419-021-03663-2.
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy that is primarily detected at the metastatic stage. Most HGSOC originates from the fallopian tube epithelium (FTE) and metastasizes to the ovary before invading the peritoneum; therefore, it is crucial to study disease initiation and progression using FTE-derived models. We previously demonstrated that loss of PTEN from the FTE leads to ovarian cancer. In the present study, loss of PTEN in FTE led to the enrichment of cancer stem cell markers such as LGR5, WNT4, ALDH1, CD44. Interestingly, loss of the transcription factor PAX2, which is a common and early alteration in HGSOC, played a pivotal role in the expression of cancer stem-like cells (CSC) markers and cell function. In addition, loss of PTEN led to the generation of two distinct subpopulations of cells with different CSC marker expression, tumorigenicity, and chemoresistance profiles. Taken together, these data suggest that loss of PTEN induces reprogramming of the FTE cells into a more stem-like phenotype due to loss of PAX2 and provides a model to study early events during the FTE-driven ovarian cancer tumor formation.
高级别浆液性卵巢癌（HGSOC）是最致命的妇科恶性肿瘤，主要在转移阶段被发现。大多数 HGSOC 起源于输卵管上皮（FTE），在侵犯腹膜之前转移到卵巢；因此，使用源自 FTE 的模型研究疾病的起始和进展至关重要。我们之前证明 FTE 中 PTEN 的缺失会导致卵巢癌。在本研究中，FTE 中 PTEN 的缺失导致癌症干细胞标志物如 LGR5、WNT4、ALDH1、CD44 的富集。有趣的是，转录因子 PAX2 的缺失，这是 HGSOC 中常见的早期改变，在癌干细胞样细胞（CSC）标志物的表达和细胞功能中起着关键作用。此外，PTEN 的缺失导致具有不同 CSC 标志物表达、致瘤性和化疗耐药性特征的两个不同细胞亚群的产生。综上所述，这些数据表明，由于 PAX2 的缺失，PTEN 的缺失导致 FTE 细胞重新编程为更类似于干细胞的表型，并提供了一个模型来研究 FTE 驱动的卵巢癌肿瘤形成过程中的早期事件。
