Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis

Ovarian cancer (OC) is highly lethal and heterogeneous. Several hormones are involved in OC etiology including estrogens; however, their role in OC is not completely understood. Here, we performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC), OVSAHO, Kura...

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Main Authors: Renata Pavlič, Marija Gjorgoska, Tea Lanišnik Rižner
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/11/2583
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author Renata Pavlič
Marija Gjorgoska
Tea Lanišnik Rižner
author_facet Renata Pavlič
Marija Gjorgoska
Tea Lanišnik Rižner
author_sort Renata Pavlič
collection DOAJ
description Ovarian cancer (OC) is highly lethal and heterogeneous. Several hormones are involved in OC etiology including estrogens; however, their role in OC is not completely understood. Here, we performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC), OVSAHO, Kuramochi, COV632, and immortalized normal ovarian epithelial HIO-80 cells. We compared these data with public transcriptome and proteome data for the HGSOC tissues. In all model systems, high steroid sulfatase expression and weak/undetected aromatase (<i>CYP19A1</i>) expression indicated the formation of estrogens from the precursor estrone-sulfate (E1-S). In OC cells, the metabolism of E1-S to estradiol was the highest in OVSAHO, followed by Kuramochi and COV362 cells, and decreased with increasing chemoresistance. In addition, higher <i>HSD17B14</i> and <i>CYP1A2</i> expressions were observed in highly chemoresistant COV362 cells and platinum-resistant tissues compared to those in HIO-80 cells and platinum-sensitive tissues. The HGSOC cell models differed in <i>HSD17B10</i>, <i>CYP1B1</i>, and <i>NQO1</i> expression. Proteomic data also showed different levels of HSD17B10, CYP1B1, NQO1, and SULT1E1 between the four HGSOC subtypes. These results suggest that different HGSOC subtypes form different levels of estrogens and their metabolites and that the estrogen-biosynthesis-associated targets should be further studied for the development of personalized treatment.
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spelling doaj.art-47fd968f64ef481b9bbbf4bb2b4e55be2023-11-23T13:47:42ZengMDPI AGCancers2072-66942022-05-011411258310.3390/cancers14112583Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen BiosynthesisRenata Pavlič0Marija Gjorgoska1Tea Lanišnik Rižner2Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaOvarian cancer (OC) is highly lethal and heterogeneous. Several hormones are involved in OC etiology including estrogens; however, their role in OC is not completely understood. Here, we performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC), OVSAHO, Kuramochi, COV632, and immortalized normal ovarian epithelial HIO-80 cells. We compared these data with public transcriptome and proteome data for the HGSOC tissues. In all model systems, high steroid sulfatase expression and weak/undetected aromatase (<i>CYP19A1</i>) expression indicated the formation of estrogens from the precursor estrone-sulfate (E1-S). In OC cells, the metabolism of E1-S to estradiol was the highest in OVSAHO, followed by Kuramochi and COV362 cells, and decreased with increasing chemoresistance. In addition, higher <i>HSD17B14</i> and <i>CYP1A2</i> expressions were observed in highly chemoresistant COV362 cells and platinum-resistant tissues compared to those in HIO-80 cells and platinum-sensitive tissues. The HGSOC cell models differed in <i>HSD17B10</i>, <i>CYP1B1</i>, and <i>NQO1</i> expression. Proteomic data also showed different levels of HSD17B10, CYP1B1, NQO1, and SULT1E1 between the four HGSOC subtypes. These results suggest that different HGSOC subtypes form different levels of estrogens and their metabolites and that the estrogen-biosynthesis-associated targets should be further studied for the development of personalized treatment.https://www.mdpi.com/2072-6694/14/11/2583ovarian cancerhigh-grade serous ovarian carcinomaHIO-80OVSAHOKuramochiCOV362
spellingShingle Renata Pavlič
Marija Gjorgoska
Tea Lanišnik Rižner
Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
Cancers
ovarian cancer
high-grade serous ovarian carcinoma
HIO-80
OVSAHO
Kuramochi
COV362
title Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
title_full Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
title_fullStr Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
title_full_unstemmed Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
title_short Model Cell Lines and Tissues of Different HGSOC Subtypes Differ in Local Estrogen Biosynthesis
title_sort model cell lines and tissues of different hgsoc subtypes differ in local estrogen biosynthesis
topic ovarian cancer
high-grade serous ovarian carcinoma
HIO-80
OVSAHO
Kuramochi
COV362
url https://www.mdpi.com/2072-6694/14/11/2583
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AT tealanisnikrizner modelcelllinesandtissuesofdifferenthgsocsubtypesdifferinlocalestrogenbiosynthesis