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Open Access 01-12-2012 | Research

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

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

Published in: Journal of Ovarian Research | Issue 1/2012

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.

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Title: Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
Authors: Takafumi Watanabe
Toshihiro Hashimoto
Takashi Sugino
Shu Soeda
Hiroshi Nishiyama
Yutaka Morimura
Hidekazu Yamada
Steve Goodison
Keiya Fujimori
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2012
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-5-7

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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