Exploring the Characteristics of Immortalized Human Ovarian Surface Epithelial Cell Lines

Overview

Journal Heliyon

Specialty Social Sciences

Date 2025 Mar 4

PMID 40034272

Authors

Ha-Yeon Shin

Wookyeom Yang

Jue Young Kim

Ha Kyun Chang

Jongman Yoo

Woo Hee Choi

Gwan Hee Han

Hanbyoul Cho

Jae-Hoon Kim

Affiliations

Soon will be listed here.

Abstract

The origins of epithelial ovarian cancer (EOC) have long been debated, with proposed sources including ovarian surface epithelial (OSE) cells, secondary Müllerian tract structures, or fallopian tube epithelium. Despite being the second most common gynecological cancer and a leading cause of death in the United States, in vitro cell models mimicking normal ovarian epithelial cells and their malignant counterparts are lacking. To address this gap, we established immortalized human OSE (IHOSE) cell lines that demonstrate stable in vitro growth without malignant properties. IHOSE cell lines were unique cell lines by analyzing short tandem repeat (STR) profiling. In addition, the epithelial characteristics were confirmed by cytokeratin 7 and cytokeratin 18 marker expression. IHOSE cell lines were subjected to Opal multiplex immunohistochemistry (IHC) analysis, which established four distinct subtypes based on marker dominance. These studies offer the most basic but essential cellular characterization information for IHOSE cell lines, providing critical data that can guide the selection of cells when inducing normal controls or disease models.

References

Auersperg N, Pan J, Grove B, Peterson T, Fisher J, Maines-Bandiera S . E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. Proc Natl Acad Sci U S A. 1999; 96(11):6249-54. PMC: 26867. DOI: 10.1073/pnas.96.11.6249. View

Huang H, Chu S, Hsu C, Chen P, Ding D, Chang M . Mutagenic, surviving and tumorigenic effects of follicular fluid in the context of p53 loss: initiation of fimbria carcinogenesis. Carcinogenesis. 2015; 36(11):1419-28. DOI: 10.1093/carcin/bgv132. View

Stack E, Wang C, Roman K, Hoyt C . Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis. Methods. 2014; 70(1):46-58. DOI: 10.1016/j.ymeth.2014.08.016. View

Komatsu H, Okawa M, Kazuki Y, Kazuki K, Hichiwa G, Shimoya K . Characterization of immortalized ovarian epithelial cells with BRCA1/2 mutation. Hum Cell. 2024; 37(4):986-996. DOI: 10.1007/s13577-024-01064-z. View

Heaphy C, Bisoffi M, Fordyce C, Haaland C, Hines W, Joste N . Telomere DNA content and allelic imbalance demonstrate field cancerization in histologically normal tissue adjacent to breast tumors. Int J Cancer. 2006; 119(1):108-16. DOI: 10.1002/ijc.21815. View

Zhang S, Dolgalev I, Zhang T, Ran H, Levine D, Neel B . Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma. Nat Commun. 2019; 10(1):5367. PMC: 6879755. DOI: 10.1038/s41467-019-13116-2. View

Tsao S, Mok S, Fey E, Fletcher J, Wan T, Chew E . Characterization of human ovarian surface epithelial cells immortalized by human papilloma viral oncogenes (HPV-E6E7 ORFs). Exp Cell Res. 1995; 218(2):499-507. DOI: 10.1006/excr.1995.1184. View

Shin H, Yang W, Lee E, Han G, Cho H, Chay D . Establishment of five immortalized human ovarian surface epithelial cell lines via SV40 T antigen or HPV E6/E7 expression. PLoS One. 2018; 13(10):e0205297. PMC: 6175519. DOI: 10.1371/journal.pone.0205297. View

Vandereyken K, Sifrim A, Thienpont B, Voet T . Methods and applications for single-cell and spatial multi-omics. Nat Rev Genet. 2023; 24(8):494-515. PMC: 9979144. DOI: 10.1038/s41576-023-00580-2. View

10.

Park Y, Jung J, Yu Z, Asaka R, Shen W, Wang Y . A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening. Lab Invest. 2021; 101(11):1505-1512. PMC: 8720294. DOI: 10.1038/s41374-021-00624-3. View

11.

Prat J . Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012; 460(3):237-49. DOI: 10.1007/s00428-012-1203-5. View

12.

Willemsen M, Krebbers G, Bekkenk M, Teunissen M, Luiten R . Improvement of Opal Multiplex Immunofluorescence Workflow for Human Tissue Sections. J Histochem Cytochem. 2021; 69(5):339-346. PMC: 8091416. DOI: 10.1369/00221554211007793. View

13.

Li X, Wang C . From bulk, single-cell to spatial RNA sequencing. Int J Oral Sci. 2021; 13(1):36. PMC: 8593179. DOI: 10.1038/s41368-021-00146-0. View

14.

Fu Z, Taylor S, Modugno F . Lifetime ovulations and epithelial ovarian cancer risk and survival: A systematic review and meta-analysis. Gynecol Oncol. 2022; 165(3):650-663. DOI: 10.1016/j.ygyno.2022.04.001. View

15.

Bonome T, Levine D, Shih J, Randonovich M, Pise-Masison C, Bogomolniy F . A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res. 2008; 68(13):5478-86. PMC: 7039050. DOI: 10.1158/0008-5472.CAN-07-6595. View

16.

Garlisi B, Lauks S, Aitken C, Ogilvie L, Lockington C, Petrik D . The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities. Curr Oncol. 2024; 31(7):3826-3844. PMC: 11275383. DOI: 10.3390/curroncol31070283. View

17.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

18.

Shin H, Yang W, Chay D, Lee E, Chung J, Kim H . Tetraspanin 1 promotes endometriosis leading to ovarian clear cell carcinoma. Mol Oncol. 2020; 15(4):987-1004. PMC: 8024726. DOI: 10.1002/1878-0261.12884. View

19.

Smith P, Wilhelm D, Rodgers R . Development of mammalian ovary. J Endocrinol. 2014; 221(3):R145-61. DOI: 10.1530/JOE-14-0062. View

20.

Torre L, Trabert B, DeSantis C, Miller K, Samimi G, Runowicz C . Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018; 68(4):284-296. PMC: 6621554. DOI: 10.3322/caac.21456. View