Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination

Takafumi Watanabe, Toshihiro Hashimoto, Takashi Sugino, Shu Soeda, Hiroshi Nishiyama, Yutaka Morimura, Hidekazu Yamada, Steven Goodison, Keiya Fujimori

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: A crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line. Methods. Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results: After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p < 0.01). IL-1β induced mesothelial cell β1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions: These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

Original languageEnglish (US)
Article number7
JournalJournal of Ovarian Research
Volume5
Issue number1
DOIs
StatePublished - Feb 2 2012
Externally publishedYes

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CD29 Antigens
Interleukin-1
Ovarian Neoplasms
Neoplasm Metastasis
Integrins
Epithelium
Cell Line
SCID Mice
Coculture Techniques
Neutralizing Antibodies
Cell Adhesion
Neoplasms
Cohort Studies
Carcinoma
Antibodies
Genes

Keywords

  • β1 integrin
  • IL-1β
  • mesothelial cell
  • ovarian cancer
  • peritoneal dissemination

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination. / Watanabe, Takafumi; Hashimoto, Toshihiro; Sugino, Takashi; Soeda, Shu; Nishiyama, Hiroshi; Morimura, Yutaka; Yamada, Hidekazu; Goodison, Steven; Fujimori, Keiya.

In: Journal of Ovarian Research, Vol. 5, No. 1, 7, 02.02.2012.

Research output: Contribution to journalArticle

Watanabe, Takafumi ; Hashimoto, Toshihiro ; Sugino, Takashi ; Soeda, Shu ; Nishiyama, Hiroshi ; Morimura, Yutaka ; Yamada, Hidekazu ; Goodison, Steven ; Fujimori, Keiya. / Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination. In: Journal of Ovarian Research. 2012 ; Vol. 5, No. 1.
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AU - Nishiyama, Hiroshi

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N2 - Background: A crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line. Methods. Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results: After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p < 0.01). IL-1β induced mesothelial cell β1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions: These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

AB - Background: A crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line. Methods. Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results: After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p < 0.01). IL-1β induced mesothelial cell β1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions: These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

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