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

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 lin...

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Autores principales: Watanabe, Takafumi, Hashimoto, Toshihiro, Sugino, Takashi, Soeda, Shu, Nishiyama, Hiroshi, Morimura, Yutaka, Yamada, Hidekazu, Goodison, Steve, Fujimori, Keiya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293087/
https://www.ncbi.nlm.nih.gov/pubmed/22296757
http://dx.doi.org/10.1186/1757-2215-5-7
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author Watanabe, Takafumi
Hashimoto, Toshihiro
Sugino, Takashi
Soeda, Shu
Nishiyama, Hiroshi
Morimura, Yutaka
Yamada, Hidekazu
Goodison, Steve
Fujimori, Keiya
author_facet Watanabe, Takafumi
Hashimoto, Toshihiro
Sugino, Takashi
Soeda, Shu
Nishiyama, Hiroshi
Morimura, Yutaka
Yamada, Hidekazu
Goodison, Steve
Fujimori, Keiya
author_sort Watanabe, Takafumi
collection PubMed
description 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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spelling pubmed-32930872012-03-05 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, Steve Fujimori, Keiya J Ovarian Res Research 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. BioMed Central 2012-02-01 /pmc/articles/PMC3293087/ /pubmed/22296757 http://dx.doi.org/10.1186/1757-2215-5-7 Text en Copyright ©2012 Watanabe et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Watanabe, Takafumi
Hashimoto, Toshihiro
Sugino, Takashi
Soeda, Shu
Nishiyama, Hiroshi
Morimura, Yutaka
Yamada, Hidekazu
Goodison, Steve
Fujimori, Keiya
Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
title Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
title_full Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
title_fullStr Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
title_full_unstemmed Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
title_short Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
title_sort production of il1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293087/
https://www.ncbi.nlm.nih.gov/pubmed/22296757
http://dx.doi.org/10.1186/1757-2215-5-7
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