Cited by 34Cancer Cells and MetastasisOvarian cancer diagnosis and treatmentMesenchymal stem cell research

Mesothelial Cells Facilitate Cancer Stem like properties in spheroids of ovarian cancer cells

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Shishido, Akemi, Mori, Seiji, Yokoyama, Yuhki, Hamada, Yoshinosuke, Minami, Kazumasa, Qian, Yamin, Wang, Jiaqi, Hirose, Haruka +5 more·2018·Oncology Reports

Abstract

Ovarian cancer is characterized by widespread peritoneal dissemination with ascites. Spheroids observed in the ascites of ovarian cancer patients are a mixture of cancer cells and mesothelial cells. In the present study, we evaluated whether mesothelial cells exfoliated from the peritoneum facilitate tumor spheroid formation and give rise to cancer stem‑like properties in ovarian cancer cells. Spheroids from the CAOV3 and A2780 ovarian cancer cell lines grew much larger in co‑culture with mesothelial cells than in monoculture under 3D conditions. The spheroids in co‑culture displayed high Ki‑67 expression in the peripheral zone and low expression in the central zone area. The expression of CD133 emerged in the inner portion of spheroids at later time‑points (96 and 168 h), indicating that cancer cells expanded to the inner spheroid and acquired stem cell‑properties. The mRNA levels of cancer stem cell markers Dclk‑1, CD44 and Bmi‑1 significantly increased in co‑cultured CAOV3 and mesothelial cells compared to CAOV3 cells alone. Furthermore, the mesothelial cells promoted the tumorigenesis and growth of the CAOV3 cells in a mouse xenograft model compared to cancer cells alone. In conclusion, mesothelial cells promoted spheroid formation by ovarian cancer cells and facilitated cancer stem‑like properties.

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  • Three-dimensional co-culture systems of ovarian cancers and mesothelial cells, including the organotypic omental mesothelium model, have enabled the study of mechanisms driving peritoneal and omental metastasis.

    “Three-dimensional co-culture systems of ovarian cancers and mesothelial cells, including the organotypic omental mesothelium model (described in Section 5.2.4) have also enabled the study of mechanisms driving peritoneal and omental metastasis (Iwanicki et al., 2011; Henry et al., 2017; Shishido et al., 2018; Loessner et al., 2019).”

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Authors
Shishido, A., Mori, S., Yokoyama, Y., Hamada, Y., Minami, K., Qian, Y., Wang, J., Hirose, H., Wu, X., Kawaguchi, N., Nagumo, S., Matsuura, N., & Yamamoto, H.
Affiliations
  • The University of Osaka (JP)
  • Morinomiya University of Medical Sciences (JP)
  • Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan
Venue
Oncology Reports
Published
2018-07-27
Volume
40
Issue
4
Pages
2105-2114
ISSN
  • 1021-335X (ISSN-L)
  • 1791-2431
OpenAlex
W2885012433
Cited by
34
References
32
Citations by year
2025: 3 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 1
FWCI
1.42
Type
journal article
Language
en
Open access
Locations
  • Oncology Reports (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (18K15318, 17K08775)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
ovarian cancer, mesothelial cells, cancer stem cells, tumor spheroids, peritoneal carcinomatosis, ascites, co-culture, CD133, DCLK1, CD44, BMI1, Ki-67, xenograft tumorigenesis, CAOV3 cells, A2780 cells
MeSH terms
Animals, Epithelium, Female, Humans, Male, Ovarian Neoplasms, Peritoneal Neoplasms, Tumor Cells, Cultured, Biomarkers, Tumor, Neoplastic Stem Cells, Mice, SCID, Rats, Sprague-Dawley, Apoptosis, Spheroids, Cellular, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Rats

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