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Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer

Uno, Kaname LU orcid ; Koya, Yoshihiro ; Yoshihara, Masato ; Iyoshi, Shohei ; Kitami, Kazuhisa ; Sugiyama, Mai ; Miyamoto, Emiri ; Mogi, Kazumasa ; Fujimoto, Hiroki and Yamakita, Yoshihiko , et al. (2024) In International Journal of Molecular Sciences 25(3).
Abstract

Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell–cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed... (More)

Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell–cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cancer spheroids, cell–cell interaction, chondroitin sulfate, ovarian cancer, peritoneal metastasis
in
International Journal of Molecular Sciences
volume
25
issue
3
article number
1626
publisher
MDPI AG
external identifiers
  • pmid:38338902
  • scopus:85184730999
ISSN
1661-6596
DOI
10.3390/ijms25031626
language
English
LU publication?
yes
id
41c5119a-2ca5-43ad-9b8e-93294e8dbcae
date added to LUP
2024-02-26 13:51:48
date last changed
2024-04-25 21:59:14
@article{41c5119a-2ca5-43ad-9b8e-93294e8dbcae,
  abstract     = {{<p>Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell–cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation.</p>}},
  author       = {{Uno, Kaname and Koya, Yoshihiro and Yoshihara, Masato and Iyoshi, Shohei and Kitami, Kazuhisa and Sugiyama, Mai and Miyamoto, Emiri and Mogi, Kazumasa and Fujimoto, Hiroki and Yamakita, Yoshihiko and Wang, Xinhui and Nawa, Akihiro and Kajiyama, Hiroaki}},
  issn         = {{1661-6596}},
  keywords     = {{cancer spheroids; cell–cell interaction; chondroitin sulfate; ovarian cancer; peritoneal metastasis}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer}},
  url          = {{http://dx.doi.org/10.3390/ijms25031626}},
  doi          = {{10.3390/ijms25031626}},
  volume       = {{25}},
  year         = {{2024}},
}