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

Journal of Ovarian Research

Keiya Fujimori³  Steve Goodison²  Hidekazu Yamada³  Yutaka Morimura¹  Hiroshi Nishiyama³  Shu Soeda³  Takashi Sugino⁴  Toshihiro Hashimoto¹  Takafumi Watanabe³ 

[1] Department of Gynecology, Tsuboi Cancer Center Hospital, Koriyama, Japan;Cancer Research Institute, M. D. Anderson Cancer Center Orlando, Orlando, FL, USA;Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima, Japan;Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan

关键词: mesothelial cell;    β1 integrin;    IL-1β;    peritoneal dissemination;    ovarian cancer;   

Others  :  815152
DOI  :  10.1186/1757-2215-5-7

 received in 2011-12-21, accepted in 2012-02-01,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Watanabe et al; licensee BioMed Central Ltd.

【 图 表 】

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