Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response

The pleiotropic adipokine chemerin affects tumor growth primarily as anti-tumoral chemoattractant inducing immunocyte recruitment. However, little is known about its effect on ovarian adenocarcinoma. In this study, we examined chemerin actions on ovarian cancer cell lines in vitro and intended to el...

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Main Authors: Meike Schmitt, Johanna Gallistl, Susanne Schüler-Toprak, Jürgen Fritsch, Christa Buechler, Olaf Ortmann, Oliver Treeck
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/17/4108
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author Meike Schmitt
Johanna Gallistl
Susanne Schüler-Toprak
Jürgen Fritsch
Christa Buechler
Olaf Ortmann
Oliver Treeck
author_facet Meike Schmitt
Johanna Gallistl
Susanne Schüler-Toprak
Jürgen Fritsch
Christa Buechler
Olaf Ortmann
Oliver Treeck
author_sort Meike Schmitt
collection DOAJ
description The pleiotropic adipokine chemerin affects tumor growth primarily as anti-tumoral chemoattractant inducing immunocyte recruitment. However, little is known about its effect on ovarian adenocarcinoma. In this study, we examined chemerin actions on ovarian cancer cell lines in vitro and intended to elucidate involved cell signaling mechanisms. Employing three ovarian cancer cell lines, we observed differentially pronounced effects of this adipokine. Treatment with chemerin (huChem-157) significantly reduced OVCAR-3 cell numbers (by 40.8% on day 6) and decreased the colony and spheroid growth of these cells by half. The spheroid size of SK-OV-3 ovarian cancer cells was also significantly reduced upon treatment. Transcriptome analyses of chemerin-treated cells revealed the most notably induced genes to be interferon alpha (IFNα)-response genes like IFI27, OAS1 and IFIT1 and their upstream regulator IRF9 in all cell lines tested. Finally, we found this adipokine to elevate IFNα levels about fourfold in culture medium of the employed cell lines. In conclusion, our data for the first time demonstrate IFNα as a mediator of chemerin action in vitro. The observed anti-tumoral effect of chemerin on ovarian cancer cells in vitro was mediated by the notable activation of IFNα response genes, resulting from the chemerin-triggered increase of secreted levels of this cytokine.
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spelling doaj.art-292e54fca6bf449788a0137ba45a0e0e2023-11-23T12:49:59ZengMDPI AGCancers2072-66942022-08-011417410810.3390/cancers14174108Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha ResponseMeike Schmitt0Johanna Gallistl1Susanne Schüler-Toprak2Jürgen Fritsch3Christa Buechler4Olaf Ortmann5Oliver Treeck6Department of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Infection Prevention and Infectious Diseases, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Internal Medicine I, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyThe pleiotropic adipokine chemerin affects tumor growth primarily as anti-tumoral chemoattractant inducing immunocyte recruitment. However, little is known about its effect on ovarian adenocarcinoma. In this study, we examined chemerin actions on ovarian cancer cell lines in vitro and intended to elucidate involved cell signaling mechanisms. Employing three ovarian cancer cell lines, we observed differentially pronounced effects of this adipokine. Treatment with chemerin (huChem-157) significantly reduced OVCAR-3 cell numbers (by 40.8% on day 6) and decreased the colony and spheroid growth of these cells by half. The spheroid size of SK-OV-3 ovarian cancer cells was also significantly reduced upon treatment. Transcriptome analyses of chemerin-treated cells revealed the most notably induced genes to be interferon alpha (IFNα)-response genes like IFI27, OAS1 and IFIT1 and their upstream regulator IRF9 in all cell lines tested. Finally, we found this adipokine to elevate IFNα levels about fourfold in culture medium of the employed cell lines. In conclusion, our data for the first time demonstrate IFNα as a mediator of chemerin action in vitro. The observed anti-tumoral effect of chemerin on ovarian cancer cells in vitro was mediated by the notable activation of IFNα response genes, resulting from the chemerin-triggered increase of secreted levels of this cytokine.https://www.mdpi.com/2072-6694/14/17/4108ovarian cancercell linechemerinadipokineinterferon alpha
spellingShingle Meike Schmitt
Johanna Gallistl
Susanne Schüler-Toprak
Jürgen Fritsch
Christa Buechler
Olaf Ortmann
Oliver Treeck
Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response
Cancers
ovarian cancer
cell line
chemerin
adipokine
interferon alpha
title Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response
title_full Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response
title_fullStr Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response
title_full_unstemmed Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response
title_short Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response
title_sort anti tumoral effect of chemerin on ovarian cancer cell lines mediated by activation of interferon alpha response
topic ovarian cancer
cell line
chemerin
adipokine
interferon alpha
url https://www.mdpi.com/2072-6694/14/17/4108
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