Interaction of ERα and NRF2 Impacts Survival in Ovarian Cancer Patients

Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cytoprotective antioxidant processes. In this study, the prognostic potential of NRF2 and its interactions with the estrogen receptor α (ERα) in ovarian cancer cells was investigated. NRF2 and ERα protein expression in ovarian cancer tissue was analyzed as well as mRNA expression of NRF2 (NFE2L2) and ERα (ESR1) in four ovarian cancer and one benign cell line. NFE2L2 silencing was carried out to evaluate a potential interplay between NRF2 and ERα. Cytoplasmic NRF2 expression as inactive form had significantly higher expression in patients with low-grade histology (p = 0.03). In the serous cancer subtype, high cytoplasmic NRF2 expression (overall survival (OS), median 50.6 vs. 29.3 months; p = 0.04) and high ERα expression (OS, median 74.5 vs. 27.1 months; p = 0.002) was associated with longer overall survival as well as combined expression of both inactive cytoplasmic NRF2 and ERα in the whole cohort (median 74.5 vs. 37.7 months; p = 0.04). Cytoplasmic NRF2 expression showed a positive correlation with ERα expression (p = 0.004). NFE2L2 was found to be highly expressed in the ovarian cancer cell lines OVCAR3, UWB1.289, and TOV112D. Compared with the benign cell line HOSEpiC, ESR1 expression was reduced in all ovary cancer cell lines (all p < 0.001). Silencing of NFE2L2 induced a higher mRNA expression of ESR1 in the NFE2L2 downregulated cancer cell lines OVCAR3 (p = 0.003) and ES2 (p < 0.001), confirming genetic interactions of NRF2 and ERα. In this study, both inactive cytoplasmic NRF2 and high ERα expression were demonstrated to be associated with improved survival in ovarian cancer patients. Further understanding of interactions within the estradiol–ERα–NRF2 pathway could better predict the impact of endocrine therapy in ovarian cancer.

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Abstract B23: CDK4/6 and MEK inhibitor combination in low-grade serous ovarian cancer cell lines

10.1158/1557-3265.ovca19-b23 ◽

2020 ◽

Author(s):

Joshua Hoenisch ◽

Hannah Kim ◽

Amy Dawson ◽

Nicole Lam ◽

Dane A. Cheasley ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Mek Inhibitor ◽

Cancer Cell Lines ◽

Low Grade ◽

Serous Ovarian Cancer ◽

Ovarian Cancer Cell Lines ◽

Inhibitor Combination

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ID: 45: EVALUATION OF CELLULAR MECHANISMS BY WHICH CINOBUFOTALIN INHIBITS OVARIAN CANCER CELL LINES FUNCTION

Journal of Investigative Medicine ◽

10.1136/jim-2016-000120.77 ◽

2016 ◽

Vol 64 (4) ◽

pp. 950.1-950 ◽

Cited By ~ 1

Author(s):

SH Afroze ◽

DC Zawieja ◽

R Tobin ◽

C Peddaboina ◽

MK Newell-Rogers ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cells ◽

Ovarian Cancer Cell Lines

ObjectiveCinobufotalin (CINO), a cardiotonic steroid (CTS) or bufadienolide, is extracted from the skin secretions of the traditional Chinese medicine giant toads (Chan su). CINO has been used as a cardiotonic, diuretic and a hemostatic agent. Previously we have shown that CINO inhibits the cytotrophoblast cell function. Recently other study has shown that CINO inhibits A549, a lung cancer cell function. In this study, we assessed the effect of CINO on three different ovarian cancer cell lines; SK-OV-3, CRL-1978 and CRL-11731 to confirm whether the effect of CINO is cell specific.Study DesignWe evaluated the effect of CINO on three ovarian cancer cells SK-OV-3, CRL-1978, and CRL-11731 function in vitro. Each Cell lines were treated with different concentrations of CINO (0.1, 1, 5 and 10 µM). For each cell line cell proliferation, migration and invasion were measured by using a CellTiter Assay (Promega), Cytoselect Assay (Cell Biolabs) and by using a FluoroBlock Assay (BD) respectively. Proliferating Cell Nuclear Antigen (PCNA) was also evaluated in cell lysates of CINO treated these 3 ovarian cancer cells by western blot analysis. Cell Cycle arrest and Cell viability were determined by fluorescence-activated cell sorting (FACS) analysis. We also performed Annexin V staining on CINO treated these 3 ovarian cancer cell lines by immunofluorescence to evaluate the pro-apoptotic protein expression. In addition mitochondrial membrane potential has also been measured for all these 3 ovarian cell lines after CINO treatment using MMP kit, by FACS analysis.ResultsConcentration of CINO at 0.5 µM inhibit SK-OV-3, CRL-1978, and CRL-11731 ovarian cancer cells proliferation, migration and invasion without cell death and loss of cell viability but cell viability differs for each cell line. Each cell lines differ in response to CINO doses for PCNA expression as well as Annexin V pro-apoptotic protein expression. CINO decreases mitochondrial membrane potential for SK-OV-3 but for CRL-1978 and CRL-11731 increases in response to CINO treatment.ConclusionCINO is cell specific, as each cancer cell line responds differently. These data demonstrate that the mode of action of CINO is different on these 3 types of ovarian cancer cells.

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Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression

International Immunology ◽

10.1093/intimm/dxz074 ◽

2019 ◽

Vol 32 (3) ◽

pp. 175-186 ◽

Cited By ~ 2

Author(s):

Hiraku Endo ◽

Naoki Hama ◽

Muhammad Baghdadi ◽

Kozo Ishikawa ◽

Ryo Otsuka ◽

...

Keyword(s):

Ovarian Cancer ◽

Disease Progression ◽

Cancer Patients ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ovarian Cancer Cell Lines ◽

Cancer Tissues ◽

The Impact

Abstract Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.

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Mutually exclusive antiproliferative effect of cell line‐specific HOX inhibition in epithelial ovarian cancer cell lines: SKOV‐3 vs RMUG‐S

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.14993 ◽

2020 ◽

Vol 24 (5) ◽

pp. 3246-3251 ◽

Cited By ~ 2

Author(s):

Miseon Kim ◽

Dong Hoon Suh ◽

Jin Young Choi ◽

Seul Lee ◽

Jae Ryul Bae ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Antiproliferative Effect ◽

Epithelial Ovarian Cancer Cell ◽

Ovarian Cancer Cell Lines

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Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8

International Journal of Molecular Sciences ◽

10.3390/ijms19072080 ◽

2018 ◽

Vol 19 (7) ◽

pp. 2080 ◽

Cited By ~ 6

Author(s):

Patrycja Tudrej ◽

Magdalena Olbryt ◽

Ewa Zembala-Nożyńska ◽

Katarzyna Kujawa ◽

Alexander Cortez ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

High Grade ◽

Serous Ovarian Cancer ◽

Ovarian Cancer Cell Lines

High-grade serous ovarian carcinoma (HGSOC) is the most frequent histological type of ovarian cancer and the one with worst prognosis. Unfortunately, the majority of established ovarian cancer cell lines which are used in the research have unclear histological origin and probably do not represent HGSOC. Thus, new and reliable models of HGSOC are needed. Ascitic fluid from a patient with recurrent HGSOC was used to establish a stable cancer cell line. Cells were characterized by cytogenetic karyotyping and short tandem repeat (STR) profiling. New generation sequencing was applied to test for hot-spot mutations in 50 cancer-associated genes and fluorescence in situ hybridization (FISH) analysis was used to check for TP53 status. Cells were analyzed for expression of several marker genes/proteins by reverse-transcription polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS), and immunocytochemistry (ICC). Functional tests were performed to compare OVPA8 cells with five commercially available and frequently used ovarian cancer cell lines: SKOV3, A2780, OVCAR3, ES2, and OAW42. Our newly-established OVPA8 cell line shows morphologic and genetic features consistent with HGSOC, such as epithelial morphology, multiple chromosomal aberrations, TP53 mutation, BRCA1 mutation, and loss of one copy of BRCA2. The OVPA8 line has a stable STR profile. Cells are positive for EpCAM, CK19, and CD44; they have relatively low plating efficiency/ability to form spheroids, a low migration rate, and intermediate invasiveness in matrigel, as compared to other ovarian cancer lines. OVPA8 is sensitive to paclitaxel and resistant to cisplatin. We also tested two FGFR inhibitors; OVPA8 cells were resistant to AZD4547 (AstraZeneca, London, UK), but sensitive to the new inhibitor CPL304-110-01 (Celon Pharma, Łomianki/Kiełpin, Poland). We have established and characterized a novel cell line, OVPA8, which can be a valuable preclinical model for studies on high-grade serous ovarian cancer.

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157 Quantitative MRNA expression of ADAMTS-1, -4, -5, -9, 15 and -20, and TIMP-3 by prostate cancer cell lines and androgen regulation in the androgen dependent cell line

European Urology Supplements ◽

10.1016/s1569-9056(04)90158-3 ◽

2004 ◽

Vol 3 (2) ◽

pp. 42

Author(s):

S. Chandrasekharan ◽

N. Cross ◽

F. Hamdy ◽

D. Buttle

Keyword(s):

Prostate Cancer ◽

Mrna Expression ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines ◽

Dependent Cell ◽

Androgen Regulation

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ADAM17—A Potential Blood-Based Biomarker for Detection of Early-Stage Ovarian Cancer

Cancers ◽

10.3390/cancers13215563 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5563

Author(s):

Christoph Rogmans ◽

Jan Dominik Kuhlmann ◽

Gerrit Hugendieck ◽

Theresa Link ◽

Norbert Arnold ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Cell Lines ◽

Ascitic Fluid ◽

Cancer Cell ◽

Culture Supernatant ◽

Ovarian Cancer Cell ◽

Cancer Cell Lines ◽

Ca 125 ◽

Ovarian Cancer Cell Lines

Ovarian cancer has the highest mortality rate among gynecological tumors. This is based on late diagnosis and the lack of early symptoms. To improve early detection, it is essential to find reliable biomarkers. The metalloprotease ADAM17 could be a potential marker, as it is highly expressed in many solid tumors, including ovarian and breast cancer. The aim of this work is to evaluate the relevance of ADAM17 as a potential diagnostic blood-based biomarker in ovarian cancer. Ovarian cancer cell lines IGROV-1 and A2780, as well as primary patient-derived tumor cells obtained from tumor tissue and ascitic fluid, were cultured to analyze ADAM17 abundance in the culture supernatant. In a translational approach, a cohort of 117 well-characterized ovarian cancer patients was assembled and ADAM17 levels in serum and corresponding ascitic fluid were determined at primary diagnosis. ADAM17 was quantified by enzyme-linked immunosorbent assay (ELISA). In the present study, ADAM17 was detected in the culture supernatant of ovarian cancer cell lines and primary cells. In addition, ADAM17 was found in serum and ascites of ovarian cancer patients. ADAM17 level was significantly increased in ovarian cancer patients compared to an age-matched control group (p < 0.0001). Importantly early FIGO I/II stages, which would not have been detected by CA-125, were associated with higher ADAM17 concentrations (p = 0.007). This is the first study proposing ADAM17 as a serum tumor marker in the setting of a gynecological tumor disease. Usage of ADAM17 in combination with CA-125 and other markers could help detect early stages of ovarian cancer.

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