PhD Scientific Days 2023

Pathology I.

The Significance of LPA-Induced Death Receptor 6 Expression in Tumor Cell Cytokine Release

Előadó neve

Dr. Enikő, Major

Neptun code

IG9PPT

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36305342593

Előadó e-mail címe

majoreniko94@gmail.com

Az előadás címe

The Significance of LPA-Induced Death Receptor 6 Expression in Tumor Cell Cytokine Release

Szerző(k) neve és munkahelye

Enikő Major1, Kuan-Hung Lin3, Krisztina Káldi2, Gábor Tigyi1,3, Zoltán Benyó1,4
1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2Department of Physiology, Semmelweis University, Budapest, Hungary
3Department of Physiology, University of Tennessee Health Science Centre, Memphis, Tennessee, USA
4Eötvös Lóránd Research Network, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Pathology I.

Language of the presentation

English

Preferred session

Pathology and Oncology

Összefoglaló szövege

Introduction: The effects of lysophosphatidic acid (LPA) are mediated by six subtypes of LPA receptors, which are expressed in various cells of the body as well as in tumor cells. In addition, tumor cells can produce LPA and induce its release from activated platelets. Interestingly, autotaxin, a lysophospholipase enzyme that catalyzes LPA synthesis, was first isolated from melanoma, and its high expression plays a role in tumor formation and progression. Furthermore, it is proven that LPA can regulate the inflammatory response in various cancers. We aimed to examine the effect of LPA on death receptor 6 (DR6) expression and cytokine release, which may have a role in tumor progression.
Methods: To investigate the effect of LPA on DR6 expression of the tumor cells, A375 and SKOV3 cells were treated with different concentrations of 18:1 LPA. Gene expression was measured by qPCR and cytokine release by ELISA. siRNAs were used for analyzing the signaling pathway of LPA-induced cytokine release. To determine the effect of LPA on DR6 promoter activity, luciferase assay was performed using HEK293T cells transfected with human DR6 promoter. In each cell line, the expression of LPA receptor subtypes was determined using qPCR. AM095 and Ki16425 were used as a specific pharmacological inhibitors of LPA receptor 1/3.
Results: We found that LPA significantly increased the promoter activity of DR6, which effect was inhibited either with AM095 or Ki16425. In A375 és SKOV3 cells, the LPA treatment resulted in an increased cytokine expression and release, while in tumor cells transfected with siDR6 or treated with AM095 or Ki16425, the effect of LPA on cytokine response was attenuated.
Conclusion: Our results indicate that LPA can induce cytokine release via DR6 upregulation.
Funding: This study was supported by NKFIH K-125174, K-135683, and K-139230 as well as by 2020-1.1.6-JÖVŐ-2021-00010, TKP2021-EGA-25 and EFOP-3.6.3-VEKOP-16-2017-00009 grants and the Richter Gedeon Talentum Foundation.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Dr. Zoltán Benyó

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7454

Start

10:00

End

10:15

Authors (legacy)

Enikő Major1, Kuan-Hung Lin3, Krisztina Káldi2, Gábor Tigyi1,3, Zoltán Benyó1,4
1Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2Department of Physiology, Semmelweis University, Budapest, Hungary
3Department of Physiology, University of Tennessee Health Science Centre, Memphis, Tennessee, USA
4Eötvös Lóránd Research Network, Budapest, Hungary