Detachment from the primary site and suspension in ascites as the initial step in metabolic reprogramming and metastasis to the omentum in ovarian cancer
Detachment from the primary site and suspension in ascites as the initial step in metabolic reprogramming and metastasis to the omentum in ovarian cancer
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DOI：
10.3892/ol.2017.7388
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发表时间：
2018-01-01
期刊：
影响因子：
2.9
通讯作者：
Fujii, Tomoyuki
中科院分区：
文献类型：
--
作者：
Sato, Masakazu;Kawana, Kei;Fujii, Tomoyuki
癌细胞的代谢目前被认为是与环境相关的，代谢重新编程正在被广泛研究。众所周知，卵巢癌常常转移到大网膜。鉴于大网膜本身含有高浓度的脂肪细胞，卵巢癌被认为是研究代谢重新编程(特别是向脂类代谢的转变)的良好模型。本研究探讨了卵巢癌细胞代谢重编程过程中向脂类代谢的转变。本研究首先考虑了表观遗传学参与的可能性。使用开放的数据库(GSE 85293和GSE 2109)，比较原发肿瘤部位(卵巢)和转移肿瘤部位(大网膜)的甲基化状态和基因表达模式。然而，没有证据表明表观遗传学(至少在DNA甲基化方面)的参与。然后考虑腹水中混悬液对代谢的影响，并采用悬浮培养作为体外模型。研究表明，从原发部位分离并悬浮在腹水中的卵巢癌细胞具有增强脂质代谢的作用。此外，研究表明，这些细胞在接近大网膜时平衡地表达高水平的肿瘤干细胞(CSC)标记物分化簇44和c-kit。因此，这些细胞激活哺乳动物雷帕霉素途径的靶点，这被认为有利于癌细胞的转移。总而言之，本研究提出了一种解释为什么卵巢癌细胞可能扩散到腹膜腔，特别是大网膜。
Cancer cell metabolism is currently considered to be context dependent, and metabolic reprogramming is being widely investigated. It is known that ovarian cancer often metastasizes to the omentum. Given that the omentum itself contains a high concentration of adipocytes, ovarian cancer is thought to be a good model for research into metabolic reprogramming (particularly the shift to lipid metabolism). The present study investigated the switch to lipid metabolism in the metabolic reprogramming of ovarian cancer cells. The present study first considered the possibility of epigenetic involvement. Using an open database (GSE 85293 and GSE2109), the methylation status and gene expression patterns of the primary tumor site (ovary) and the metastatic tumor site (omentum) were compared. However, no evidence was obtained regarding the involvement of epigenetics (at least in terms of DNA methylation). The influence of suspension in ascites on metabolism was then considered, and a suspension culture was used as an in vitro model. It was demonstrated that ovarian cancer cells that are detached from the primary site and suspended in ascites have enhanced lipid metabolism. Additionally, it was demonstrated that these cells express high levels of the cancer stem cell (CSC) marker cluster of differentiation 44 and c-kit in a balanced manner as they approach the omentum. Accordingly, these cells activate the mammalian target of rapamycin pathway, which is thought to be advantageous for cancer cell metastasis. In conclusion, the present study proposed one explanation for why ovarian cancer cells are likely to disseminate to the peritoneal cavity, and in particular to the omentum.