Abstract
A cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III). We identify a 67-protein cell line signature, which separates our entire proteomic data set, as well as a confirmatory publicly available CPTAC/TCGA tumour proteome data set, into a predominantly epithelial and mesenchymal HGSOC tumour cluster. This proteomics-based epithelial/mesenchymal stratification of cell lines and human tumours indicates a possible origin of HGSOC either from the fallopian tube or from the ovarian surface epithelium.
Highlights
A cell line representative of human high-grade serous ovarian cancer (HGSOC) should resemble its tumour of origin at the molecular level, and demonstrate functional utility in pre-clinical investigations
We quantified the proteomes of eight HGSOC tumour tissues, 30 cell lines (26 ovarian cancer (OvCa); two cervical cancer; two immortalized ovarian surface epithelial (IOSE)) and three primary fallopian tube epithelial cells (FTECs) isolates (Fig. 1a)
The Label-free protein quantification (LFQ) values were highly reproducible as cell line replicates had median Pearson correlation coefficients of 0.95 (Supplementary Fig. 1a), whereas comparison of the two different IOSE cell lines and FTECs from two different healthy donors had only somewhat lower correlations of 0.93 each
Summary
A cell line representative of human high-grade serous ovarian cancer (HGSOC) should resemble its tumour of origin at the molecular level, and demonstrate functional utility in pre-clinical investigations. We identify a 67-protein cell line signature, which separates our entire proteomic data set, as well as a confirmatory publicly available CPTAC/TCGA tumour proteome data set, into a predominantly epithelial and mesenchymal HGSOC tumour cluster This proteomics-based epithelial/mesenchymal stratification of cell lines and human tumours indicates a possible origin of HGSOC either from the fallopian tube or from the ovarian surface epithelium. We here demonstrate that directly integrating proteomic profiles from cell lines, tumour tissues and primary cells adds a highly informative level to the evaluation of OvCa cellular model systems. We provide a user-friendly resource of the quantitative protein expression of 30 ovarian cell lines
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