Wang Yunxia, Liu Peishu, Wang Xietong, Mao Hongluan
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Obstetrics and Gynaecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2017 Jul;16(1):325-330. doi: 10.3892/mmr.2017.6597. Epub 2017 May 17.
X-linked inhibitor of apoptosis‑associated factor 1 (XAF1) was identified as a novel X-linked inhibitor of apoptosis (XIAP) binding partner that may reverse the anti‑apoptotic effect of XIAP. Previous studies have revealed that XAF1 serves an important role in cancer angiogenesis. Vasculogenic mimicry (VM) describes the formation of fluid‑conducting channels by highly invasive and genetically dysregulated tumor cells. VM is critical for tumor blood supply and is associated with aggressive actions and metastasis. The aim of present study was to investigate the potential association between XAF1 expression with VM of ovarian cancer, and evaluate the role of XAF1 in tumor cell migration and invasion of SKOV3 cells. VM structure and XAF1 expression were detected in 94 tissue samples of advanced epithelial ovarian cancer (EOC). Invasion and migration of the SKOV3 human ovarian carcinoma cell line were identified by Transwell assay. It was revealed that the presence of VM was associated with high grade advanced ovarian cancer. Reduced XAF1 expression was significantly associated with presence of VM. Overexpression of XAF1 significantly reduced invasion and migration of SKOV3 cells, and inhibited vascular endothelial growth factor protein expression. Furthermore, vasculature was suppressed by overexpression of XAF1 in vivo in xenograft models. In conclusion, XAF1 expression was associated with VM in ovarian cancer, suggesting a potential role of XAF1 in the formation of VM in EOC. These findings may facilitate the development of novel therapeutic agents for the treatment of ovarian cancer.
X连锁凋亡抑制相关因子1（XAF1）被鉴定为一种新型的X连锁凋亡抑制蛋白（XIAP）结合伴侣，它可能会逆转XIAP的抗凋亡作用。先前的研究表明，XAF1在癌症血管生成中起重要作用。血管生成拟态（VM）描述了高侵袭性和基因失调的肿瘤细胞形成液体传导通道的过程。VM对肿瘤血液供应至关重要，并且与侵袭性行为和转移相关。本研究的目的是探讨XAF1表达与卵巢癌VM之间的潜在关联，并评估XAF1在SKOV3细胞肿瘤细胞迁移和侵袭中的作用。在94例晚期上皮性卵巢癌（EOC）组织样本中检测VM结构和XAF1表达。通过Transwell实验鉴定SKOV3人卵巢癌细胞系的侵袭和迁移能力。结果显示，VM的存在与高级别晚期卵巢癌相关。XAF1表达降低与VM的存在显著相关。XAF1的过表达显著降低了SKOV3细胞的侵袭和迁移能力，并抑制了血管内皮生长因子蛋白的表达。此外，在异种移植模型中，XAF1的过表达在体内抑制了血管生成。总之，XAF1表达与卵巢癌中的VM相关，提示XAF1在EOC中VM形成中具有潜在作用。这些发现可能有助于开发治疗卵巢癌的新型治疗药物。
