Penn Ovarian Cancer Research Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Sci Rep. 2023 Jan 27;13(1):1537. doi: 10.1038/s41598-023-28840-5.
Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker. Interestingly, ORF1p expression is detectable in fallopian tube (FT) epithelial precursors of HGSOC but not in benign FT, suggesting that ORF1p expression in an early event in HGSOC development. Finally, treatment of FT cells with DNA methyltransferase inhibitors led to robust expression and release of ORF1p, validating the regulatory role of DNA methylation in LINE-1 repression in non-tumorigenic tissue.
长散在元件 1(LINE-1)开放阅读框 1 蛋白(ORF1p)的表达是许多癌症类型的共同特征,包括高级别浆液性卵巢癌(HGSOC)。在这里,我们报告说,ORF1p 不仅表达,而且还被卵巢癌和原代肿瘤细胞释放。免疫多重反应监测-质谱分析表明,释放的 ORF1p 在条件培养基、腹水和患者血浆中可被可靠检测到,提示 ORF1p 是一种潜在的生物标志物。有趣的是,ORF1p 的表达可在 HGSOC 的输卵管(FT)上皮前体中检测到,但在良性 FT 中不可检测到,这表明 ORF1p 的表达是 HGSOC 发展中的早期事件。最后,用 DNA 甲基转移酶抑制剂处理 FT 细胞会导致 ORF1p 的强烈表达和释放,验证了 DNA 甲基化在非肿瘤组织中对 LINE-1 抑制的调节作用。