Abstract 3059: CCL2 overexpression in an epithelial ovarian cancer cell line results in reduced tumorigenic potential
Bibliographic record
Abstract
Abstract Chromosome 17 abnormalities are frequently observed in epithelial ovarian cancer (EOC), suggesting that one or more genes mapping to this chromosome contribute to EOC development and/or progression. We have previously performed a comparative transcriptome analysis of primary cultures of normal ovarian surface epithelial (NOSE) cells and malignant, serous subtype ovarian tumor (TOV) samples in order to identify differentially expressed chromosome 17 genes. CCL2, at 17q12, was significantly differentially underexpressed at least 3-fold in all TOV samples. We have confirmed underexpression in an independent series of 99 serous EOC tumor samples. Interestingly, CCL2 was identified as a significantly up-regulated gene occurring as a consequence of tumor suppression in the characterization of a novel EOC cell line model developed by transferring chromosome 3 fragments into the tumorigenic OV-90 EOC cell line. We have further characterized CCL2 expression in a series of EOC cell lines that differ in their tumorigenic potential, and have shown the lowest levels of gene expression occur in tumorigenic cell lines. DNA sequencing did not reveal any evidence of mutations. To determine if overexpression affects tumorigenicity or growth characteristics, we have generated stable overexpressing OV-90 clones using a commercially available pDream: CCL2 expression vector. Overexpression was verified by ELISA. In cell culture, the CCL2 overexpressing clones appeared less tightly packed and more elongated as compared with OV-90 cells. The cell viability of the CCL2 clones appears to be reduced when compared to the parental OV-90 cell line in XTT cell proliferation assays. The ability of the CCL2 clones to form colonies was also reduced as compared to OV-90 in a colony formation assay. There is also evidence of an increase in the percentage of senescent cells in the CCL2 clones based on a beta-galactosidase staining assay. Both CCL2 overexpressing clones exhibit latency in tumor formation in intraperitoneal tumorigenicity assays involving SCID mice as compared with the parental OV-90 cell line. This is the first report of stable CCL2 transfection into an EOC cell line. Our results suggest that CCL2 expression may reduce the tumorigenic potential of EOC cells, and draws attention to the role of the innate immune system and the tumor microenvironment in EOC development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3059. doi:10.1158/1538-7445.AM2011-3059
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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 | 0.000 | 0.000 |
| 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) | 0.002 | 0.001 |
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".