Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation

Uno, Kaname LU orcid ; Yoshihara, Masato ; Yamakita, Yoshihiko ; Kitami, Kazuhisa ; Iyoshi, Shohei ; Sugiyama, Mai ; Koya, Yoshihiro ; Kanayama, Tomihiro ; Saharaa, Haruhito and Nomura, Satoshi , et al. (2026) In Science Advances 12(6).
Abstract

Patients with epithelial ovarian cancer (EOC) are often diagnosed with peritoneal metastasis and ascites, the accumulation of intraperitoneal fluid containing nonmalignant cells. However, the interactions between EOC and nonmalignant cells before peritoneal metastasis remain unclear. To investigate this, whole EOC spheroids were observed using a multiphoton microscope, and their invasion ability was assessed. Mesothelial cells were identified as notable components of ascites through morphological assessment, immunohistochemical/immunofluorescence staining, and single-cell RNA sequencing analyses. Almost all EOC cells were spheroids, with 60% containing mesothelial cells. EOC cells quickly generate aggregated spheroids with mesothelial... (More)

Patients with epithelial ovarian cancer (EOC) are often diagnosed with peritoneal metastasis and ascites, the accumulation of intraperitoneal fluid containing nonmalignant cells. However, the interactions between EOC and nonmalignant cells before peritoneal metastasis remain unclear. To investigate this, whole EOC spheroids were observed using a multiphoton microscope, and their invasion ability was assessed. Mesothelial cells were identified as notable components of ascites through morphological assessment, immunohistochemical/immunofluorescence staining, and single-cell RNA sequencing analyses. Almost all EOC cells were spheroids, with 60% containing mesothelial cells. EOC cells quickly generate aggregated spheroids with mesothelial cells, and these aggregated cancer-mesothelial spheroids (ACMSs) invade collagen or mesothelial layers. Mesothelial cells forming ACMSs initiated the invasion. RNA sequencing analysis revealed marked RNA expression changes in mesothelial cells, whereas the changes in EOC cells were minor. Transforming growth factor–β1–stimulated mesothelial cells showed increased invadopodium formation along with fascin-1 up-regulation. These findings suggest that EOC cells alter mesothelial cells through ACMSs, thereby elucidating the rapid spread of EOC in the abdominal cavity.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
12
issue
6
article number
eadu5944
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:41650261
  • scopus:105029610374
ISSN
2375-2548
DOI
10.1126/sciadv.adu5944
language
English
LU publication?
yes
id
12efc8c3-8f30-4f53-85f5-aa119452768f
date added to LUP
2026-03-03 11:54:36
date last changed
2026-05-27 00:29:19
@article{12efc8c3-8f30-4f53-85f5-aa119452768f,
  abstract     = {{<p>Patients with epithelial ovarian cancer (EOC) are often diagnosed with peritoneal metastasis and ascites, the accumulation of intraperitoneal fluid containing nonmalignant cells. However, the interactions between EOC and nonmalignant cells before peritoneal metastasis remain unclear. To investigate this, whole EOC spheroids were observed using a multiphoton microscope, and their invasion ability was assessed. Mesothelial cells were identified as notable components of ascites through morphological assessment, immunohistochemical/immunofluorescence staining, and single-cell RNA sequencing analyses. Almost all EOC cells were spheroids, with 60% containing mesothelial cells. EOC cells quickly generate aggregated spheroids with mesothelial cells, and these aggregated cancer-mesothelial spheroids (ACMSs) invade collagen or mesothelial layers. Mesothelial cells forming ACMSs initiated the invasion. RNA sequencing analysis revealed marked RNA expression changes in mesothelial cells, whereas the changes in EOC cells were minor. Transforming growth factor–β1–stimulated mesothelial cells showed increased invadopodium formation along with fascin-1 up-regulation. These findings suggest that EOC cells alter mesothelial cells through ACMSs, thereby elucidating the rapid spread of EOC in the abdominal cavity.</p>}},
  author       = {{Uno, Kaname and Yoshihara, Masato and Yamakita, Yoshihiko and Kitami, Kazuhisa and Iyoshi, Shohei and Sugiyama, Mai and Koya, Yoshihiro and Kanayama, Tomihiro and Saharaa, Haruhito and Nomura, Satoshi and Mogi, Kazumasa and Miyamoto, Emiri and Fujimoto, Hiroki and Yoshida, Kosuke and Tamauchi, Satoshi and Yokoi, Akira and Yoshikawa, Nobuhisa and Niimi, Kaoru and Shiraki, Yukihiro and Sjölund, Jonas and Oguchi, Hidenori and Pietras, Kristian and Enomoto, Atsushi and Nawa, Akihiro and Tomita, Hiroyuki and Kajiyama, Hiroaki}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation}},
  url          = {{http://dx.doi.org/10.1126/sciadv.adu5944}},
  doi          = {{10.1126/sciadv.adu5944}},
  volume       = {{12}},
  year         = {{2026}},
}