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

Abstract

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.

Integrative analysis of cuproptosis‐associated genes for predicting immunotherapy response in single‐cell and multi‐cohort studies

“…It is regarded as a putative tumor suppressor gene since it is one of the frequently methylated locations in different malignancies 28,29 . IFI27 (Interferon alpha‐inducible protein 27), initially reported to mediate interferon (IFN)‐induced cell death, has recently been shown to influence cell cycle regulation, preventing cancer cells from proliferating while avoiding cell apoptosis 30 . As our multifactor Cox regression analysis results suggest, IFI27 is a patient protective factor.…”

The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer

“…Hoffmann et al [ 251 ], based on their study, concluded that the use of exogenous chemerin has no effect on both ovarian cancer cells and physiological ovarian cells. In contrast, Schmitt et al [ 252 ] noted that chemerin in vitro reduced the number of cells in the OVCAR-3 line. They also noted that chemerin affected the activation of Interferon alpha (IFNα) response genes, mainly Interferon alpha-inducible protein 27 (IFI27), 2′-5′-Oligoadenylate Synthetase 1 (OAS1), Interferon Induced Protein With Tetratricopeptide Repeats 1 (IFIT1) and Interferon Regulatory Factor 9 (IRF9), and thus affected IFNα activity.…”

Evaluation of the Potential Diagnostic Utility of the Determination of Selected Immunological and Molecular Parameters in Patients with Ovarian Cancer

“…They found that body-fat mass appears to be the main determinant of increased chemerin and decreased omentin levels in women with PCOS [105]. Schmitt M. et al [106] studied the effect of chemerin on ovarian cancer cell lines in vitro. The addition of chemerin significantly reduced the number of OVCAR-3 cells and halved the colony growth of these cells.…”