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Vitamin D derivatives inhibit mesenchymal transition of mesothelial cells and mitigate peritoneal dissemination of ovarian cancer

Fujita, Kazuhisa ; Hayashi, Maia ; Yoshihara, Masato ; Nomura, Satoshi ; Kitami, Kazuhisa ; Miyamoto, Emiri ; Iyoshi, Shohei ; Mogi, Kazumasa ; Fujimoto, Hiroki and Uno, Kaname LU orcid , et al. (2025) In Medical Molecular Morphology
Abstract

Ovarian cancer (OvCa) is a leading cause of gynecological cancer-related mortality, primarily due to peritoneal dissemination, which facilitates metastasis in the abdominal cavity. This study explored the potential of vitamin D and its synthetic derivatives in mitigating peritoneal dissemination by modulating the behavior of mesothelial cells (MCs). Vitamin D, through its receptor (VDR), is known to influence cancer progression, and our findings demonstrate that vitamin D derivatives can inhibit mesenchymal transition of MCs induced by TGF-β1, a key driver of peritoneal dissemination. This study used patient-derived primary MCs and in vivo mouse model to assess the effects of vitamin D derivatives on cell morphology, gene expression,... (More)

Ovarian cancer (OvCa) is a leading cause of gynecological cancer-related mortality, primarily due to peritoneal dissemination, which facilitates metastasis in the abdominal cavity. This study explored the potential of vitamin D and its synthetic derivatives in mitigating peritoneal dissemination by modulating the behavior of mesothelial cells (MCs). Vitamin D, through its receptor (VDR), is known to influence cancer progression, and our findings demonstrate that vitamin D derivatives can inhibit mesenchymal transition of MCs induced by TGF-β1, a key driver of peritoneal dissemination. This study used patient-derived primary MCs and in vivo mouse model to assess the effects of vitamin D derivatives on cell morphology, gene expression, and OvCa cell adhesion. Two vitamin D derivatives, VDR agonist, showed significant efficacy in maintaining epithelial-like MC morphology, reducing TGF-β1-induced changes, and inhibiting OvCa cell adhesion to the peritoneum, similar to calcitriol. Conversely, the VDR antagonist derivative induced MC apoptosis, highlighting the essential role of vitamin D in MC survival. These findings suggest that vitamin D derivatives could serve as promising therapeutic agents for OvCa by preserving peritoneal homeostasis and preventing metastasis. Further research is required to explore a broader range of derivatives and their underlying molecular mechanisms.

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publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Mesenchymal transition, Mesothelial cells, Ovarian cancer, Peritoneal dissemination, Vitamin D
in
Medical Molecular Morphology
article number
e0295288
publisher
Springer
external identifiers
  • scopus:85217921199
  • pmid:39964447
ISSN
1860-1480
DOI
10.1007/s00795-025-00424-4
language
English
LU publication?
yes
id
513e0226-5752-4bfe-aa4c-1e93897ce398
date added to LUP
2025-07-04 14:24:28
date last changed
2025-08-01 16:58:37
@article{513e0226-5752-4bfe-aa4c-1e93897ce398,
  abstract     = {{<p>Ovarian cancer (OvCa) is a leading cause of gynecological cancer-related mortality, primarily due to peritoneal dissemination, which facilitates metastasis in the abdominal cavity. This study explored the potential of vitamin D and its synthetic derivatives in mitigating peritoneal dissemination by modulating the behavior of mesothelial cells (MCs). Vitamin D, through its receptor (VDR), is known to influence cancer progression, and our findings demonstrate that vitamin D derivatives can inhibit mesenchymal transition of MCs induced by TGF-β1, a key driver of peritoneal dissemination. This study used patient-derived primary MCs and in vivo mouse model to assess the effects of vitamin D derivatives on cell morphology, gene expression, and OvCa cell adhesion. Two vitamin D derivatives, VDR agonist, showed significant efficacy in maintaining epithelial-like MC morphology, reducing TGF-β1-induced changes, and inhibiting OvCa cell adhesion to the peritoneum, similar to calcitriol. Conversely, the VDR antagonist derivative induced MC apoptosis, highlighting the essential role of vitamin D in MC survival. These findings suggest that vitamin D derivatives could serve as promising therapeutic agents for OvCa by preserving peritoneal homeostasis and preventing metastasis. Further research is required to explore a broader range of derivatives and their underlying molecular mechanisms.</p>}},
  author       = {{Fujita, Kazuhisa and Hayashi, Maia and Yoshihara, Masato and Nomura, Satoshi and Kitami, Kazuhisa and Miyamoto, Emiri and Iyoshi, Shohei and Mogi, Kazumasa and Fujimoto, Hiroki and Uno, Kaname and Kunishima, Atsushi and Yamakita, Yoshihiko and Tomita, Hiroyuki and Tsutsumi, Rino and Sakamoto, Ryota and Nagasawa, Kazuo and Masuo, Yusuke and Nishiuchi, Takumi and Shibata, Kiyosumi and Enomoto, Atsushi and Kajiyama, Hiroaki}},
  issn         = {{1860-1480}},
  keywords     = {{Mesenchymal transition; Mesothelial cells; Ovarian cancer; Peritoneal dissemination; Vitamin D}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Medical Molecular Morphology}},
  title        = {{Vitamin D derivatives inhibit mesenchymal transition of mesothelial cells and mitigate peritoneal dissemination of ovarian cancer}},
  url          = {{http://dx.doi.org/10.1007/s00795-025-00424-4}},
  doi          = {{10.1007/s00795-025-00424-4}},
  year         = {{2025}},
}