输卵管菌毛上皮(FTE)中的分泌细胞被认为是卵巢高级别浆液性癌(HGSC)的主要起源细胞。排卵是FTE肿瘤发生的主要原因,通过一系列TP53突变进行,由于Rb/细胞周期蛋白E畸变导致的染色体不稳定,原位癌(STIC),和转移到卵巢和腹膜(转移性HGSC)。以前,我们已经确定了排卵卵泡液(FF)的多种致癌活性,在转化的不同阶段对FTE细胞发挥全谱的转化活性。排卵后,FF被输入腹膜液(PF),FTE不断沐浴。我们想知道PF是否具有与FF相同的致癌活性谱,以及这些活性是否源自FF。通过使用一组具有p53突变的FTE细胞系(FT282-V),p53/CCNE1畸变(FT282-CCNE1),和p53/Rb畸变加上自发转化,和腹膜转移(FEXT2),我们分析了排卵前或后收集的FF和PF处理后不同转化表型的变化。与FF表现出的效果类似,我们发现,在较小程度上,PF促进了锚定独立生长(AIG),迁移,抗肛门病,和腹膜附着在转化FTE细胞中。越多的转化细胞通常越受影响。在PF处理表现出的转化活性中,AIG,基质胶入侵,黄体期PF治疗的腹膜附着生长高于增殖期PF治疗,提示排卵来源。相比之下,对排卵前后收集的PF处理的抗失巢凋亡和迁移活性的变化相似,暗示了一个独立于排卵的来源.在i.p.共注射异种移植小鼠模型中验证了黄体期PF的总体转化活性。Luc-FEXT2细胞与FF或黄体阶段PF共同注射支持早期腹膜植入,而与卵泡相PF共注射则没有。这项研究,第一次,表明,来自排卵妇女的PF可以在恶性转化的不同阶段促进FTE细胞中不同的致癌表型。这些活动中,除了抗肛门凋亡和细胞迁移,来源于排卵。
Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation.