Abstract B61: Proteomic profiling of ovarian cancer and mesothelial cells reveals novel mediators implicated in the metastatic progression of ovarian cancer to the peritoneum
Bibliographic record
Abstract
Abstract Over the past decade, numerous studies have highlighted the impact of the cancer microenvironment on tumor progression. It is now well understood that tumor cell behaviour is largely influenced by various stromal cell types and extracellular matrix components within their surrounding environments. A key hallmark of epithelial ovarian cancer (EOC) progression is the attachment of cancerous cells to the mesothelium and the formation of invasive peritoneal implants. Given that metastatic dissemination to the peritoneum is associated with poor prognosis, delineating the factors involved in cancer-peritoneal cell interaction, and the mechanisms they employ, is vital to improving patient survival as it may lead to the discovery of novel therapeutic targets. As such, we aimed to elucidate proteins that participate in this interaction by comparing the secreted proteome (referred to as the secretome) of an in vitro co-culture model containing ovarian cancer (OVCAR-5) and mesothelial cells (LP-9) to that of their monoculture secretomes. Using two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we identified 1584 proteins that were secreted by co-cultures, and 1644 and 1420 proteins by OVCAR-5 and LP-9 cells, respectively. After comparative analysis and application of our filtering criteria, we identified 53 proteins that were differentially secreted during cancer and mesothelial interaction, and of these, mucin 5AC (MUC5AC) displayed significantly elevated secretion in the co-culture secretomes. Relative mRNA expression of candidates was assessed using quantitative PCR, which also revealed an increase in MUC5AC gene expression in three different co-culture models (OVCAR-5 and LP-9; BG-1 and LP-9; OV-90 and LP-9) (p<0.05). Immunocytochemistry analysis also revealed increased expression of MUC5AC in ovarian cancer and peritoneal co-cultures. Taken together, these findings reveal novel proteins that may potentially regulate the progression of ovarian cancer to the peritoneum, particularly MUC5AC, and elucidation of its role in EOC warrants further investigation. Citation Format: Natasha Musrap, George S. Karagiannis, Eleftherios P. Diamandis. Proteomic profiling of ovarian cancer and mesothelial cells reveals novel mediators implicated in the metastatic progression of ovarian cancer to the peritoneum. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B61.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".