Detachment from the primary site and suspension in ascites as the initial step in metabolic reprogramming and metastasis to the omentum in ovarian cancer

Sato,Masakazu; Kawana,Kei; Adachi,Katsuyuki; Fujimoto,Asaha; Yoshida,Mitsuyo; Nakamura,Hiroe; Nishida,Haruka; Inoue,Tomoko; Taguchi,Ayumi; Ogishima,Juri; Eguchi,Satoko; Yamashita,Aki; Tomio,Kensuke; Komatsu,Atsushi; Wada‑Hiraike,Osamu; Oda,Katsutoshi; Nagamatsu,Takeshi; Osuga,Yutaka; Fujii,Tomoyuki

doi:10.3892/ol.2017.7388

January-2018 Volume 15 Issue 1

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January-2018 Volume 15 Issue 1

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Article

Detachment from the primary site and suspension in ascites as the initial step in metabolic reprogramming and metastasis to the omentum in ovarian cancer

Authors:
- Masakazu Sato
- Kei Kawana
- Katsuyuki Adachi
- Asaha Fujimoto
- Mitsuyo Yoshida
- Hiroe Nakamura
- Haruka Nishida
- Tomoko Inoue
- Ayumi Taguchi
- Juri Ogishima
- Satoko Eguchi
- Aki Yamashita
- Kensuke Tomio
- Atsushi Komatsu
- Osamu Wada‑Hiraike
- Katsutoshi Oda
- Takeshi Nagamatsu
- Yutaka Osuga
- Tomoyuki Fujii
View Affiliations / Copyright

Affiliations: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo‑ku, Tokyo 113‑8655, Japan, Department of Obstetrics and Gynecology, School of Medicine, Nihon University, Itabashi‑ku, Tokyo 173‑8610, Japan
Pages: 1357-1361
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Published online on: November 9, 2017

https://doi.org/10.3892/ol.2017.7388
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Abstract

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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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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