Xie Guangyan, Zhang Yongli, Ma Jiachen, Guo Xiaoli, Xu Jiahao, Chen Linna, Zhang Jingbo, Li Yanyu, Zhang Bei, Zhou Xueyan
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, Xuzhou, China.
Department of Obstetrics and Gynecology, the Second People's Hospital of Lianyungang, Lianyungang, China.
Transl Cancer Res. 2024 Oct 31;13(10):5365-5380. doi: 10.21037/tcr-24-789. Epub 2024 Oct 29.
The primary cause of mortality in patients with ovarian cancer (OC) is tumor metastasis. A comprehensive understanding of the mechanisms underlying metastasis in OC is essential for accurate prognosis prediction and the development of targeted therapeutic agents. Our findings indicate that alpha-2 Heremans Schmid glycoprotein (AHSG) is downregulated in OC exosomes. Consequently, the objective of this study was to identify novel prognostic markers and potential therapeutic targets for OC.
Exosomes derived from OC cells and patient ascites were purified and applied to OC cells to assess their migratory ability using wound-healing and transwell assays. AHSG expression was enhanced by overexpressing lentivirus, and the resulting exosomes were isolated and co-cultured with OC cells to verify their effect on the migration ability of OC.
Exosomes in ovarian malignant ascites have been demonstrated to promote OC metastasis. However, our findings indicate that AHSG is down-regulated in OC tissues and ascites exosomes. Furthermore, overexpression of AHSG in OC cells has been shown to markedly decrease their migratory ability, as well as reduce the migratory ability of cancer cells after co-culture of its exosomes with cancer cells.
The low expression of AHSG in exosomes derived from OC tissues and ascites is associated with metastatic progression in OC patients. Additionally, cancer-derived AHSG can be transported to OC cells via exosomes, where it inhibits OC migration and by regulating the p53/FAK/Src signaling pathway. The present study demonstrated that AHSG, derived from cancer cells, exerts a negative regulatory effect on OC cell motility, migration, and metastasis. These findings suggest that AHSG is a potential candidate for OC treatment.
卵巢癌（OC）患者死亡的主要原因是肿瘤转移。全面了解OC转移的潜在机制对于准确预测预后和开发靶向治疗药物至关重要。我们的研究结果表明，α-2赫曼斯·施密德糖蛋白（AHSG）在OC外泌体中表达下调。因此，本研究的目的是确定OC的新型预后标志物和潜在治疗靶点。
从OC细胞和患者腹水中纯化外泌体，并将其应用于OC细胞，通过伤口愈合和Transwell实验评估其迁移能力。通过过表达慢病毒增强AHSG表达，分离得到的外泌体并与OC细胞共培养，以验证其对OC迁移能力的影响。
卵巢恶性腹水中的外泌体已被证明可促进OC转移。然而，我们的研究结果表明，AHSG在OC组织和腹水外泌体中表达下调。此外，OC细胞中AHSG的过表达已被证明可显著降低其迁移能力，以及在其外泌体与癌细胞共培养后降低癌细胞的迁移能力。
OC组织和腹水中来源的外泌体中AHSG的低表达与OC患者的转移进展相关。此外，癌症来源的AHSG可通过外泌体转运至OC细胞，在其中通过调节p53/FAK/Src信号通路抑制OC迁移。本研究表明，癌细胞来源的AHSG对OC细胞的运动性、迁移和转移发挥负调节作用。这些发现表明AHSG是OC治疗的潜在候选物。
