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Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines.

ABSTRACT: In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile.

SUBMITTER: Kloudova K

PROVIDER: S-EPMC5216785 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines.

Kloudová Kamila K Hromádková Hana H Partlová Simona S Brtnický Tomáš T Rob Lukáš L Bartůňková Jiřina J Hensler Michal M Halaška Michael J MJ Špíšek Radek R Fialová Anna A

Oncotarget 20160701 29

In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelia ...[more]

PMID: 27323861

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Project description:PurposeOvarian cancer, manifested by malignant ascites, is the most lethal gynaecological cancer. Suspended ascites-derived spheroids may contribute to ovarian cancer metastasis. MicroRNAs (miRNAs) are also associated with ovarian cancer metastasis. Here, we aimed to investigate the differentially expressed miRNAs (DE-miRNAs) in ascites-derived spheroids compared with primary tumour tissues, which may regulate ovarian cancer metastasis.MethodsThe DE-miRNAs between ovarian cancer primary tumour tissues and ascites-derived spheroids were identified by GEO2R screening in samples from 3 high-grade serous ovarian cancer (HGSOC) patients of dataset GSE65819. We used MiRTarBase, TargetScanHuman7.2 and STRING to predict the target hub genes of DE-miRNAs and DAVID to perform functional analysis of hub genes. ALGGEN PROMO and TransmiR v2.0 were used to predict transcription factors (TFs) that potentially regulate DE-miRNAs expression. The observed differences in DE-miRNAs expression were validated with samples from 12 HGSOC patients and 2 ovarian cancer cell lines using PCR. The functions of DE-miRNAs on ovarian cancer progression were verified by invasion, adherent, and angiogenesis assays.ResultsThrough bioinformatics screening and experimental validation, miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p were identified as being significantly downregulated in ascites-derived spheroids compared with primary tumour tissues. In addition, TFAP2A was identified as a potentially common upstream TF regulating the expression of the above mentioned DE-miRNAs. The overexpression of miR-199a-3p, miR-199b-3p, miR-199a-5p lead to invasion inhibition, and the overexpression of miR-126-3p, miR-145-5p, miR-199a-5p and miR-199b-3p lead to adhesion inhibition of suspended ovarian cancer cells. High-expressed miR-126-3p, miR-199a-3p, miR-199a-5p and miR-199b-3p contributed to apoptosis of suspended ovarian cancer cells.ConclusionThe downregulated expression of miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p in ascites-derived spheroids plays a key role in promoting ovarian cancer progression, which may represent novel molecules for targeted therapy for ovarian cancer.

Dataset Information

Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines.

Publications

Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines.

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