Abstract 3062: Ablation of parathyroid hormone-related protein in the triple negative human breast cancer line MDA-MB-231 inhibits its cancer stem cell phenotype
Bibliographic record
Abstract
Abstract Parathyroid hormone-related protein (PTHrP) is a pleiotropic hormone involved in a wide range of developmental & physiological processes. It is also dysregulated in advanced cancers where it causes malignancy-associated hypercalcemia & plays a major role in the progression of bone metastases. We have shown previously that PTHrP ablation delays tumor initiation & that it is preferentially expressed in triple negative breast cancer (TNBC).Here we investigated how PTHrP can influence the phenotype of the human TNBC cell line MDA-MB231 using CRISPR/cas 9 knockout technology. We used U6G RNA-Cas9-2A-red fluorescence protein (RFP) vector with a human PTHrP specific guide RNA directed to exon 4(knockout/KO) or an empty vector as control. PTHrP KO cells (RFP+) were isolated using AutoMacs Pro Separator & single cells were exp&ed in 96 well plates. Positive clones were confirmed by DNA sequencing. Real time PCR & immunofluorescence staining confirmed that 5/96 KO clones had between 95-99% decrease in PTHrP expression compared to control cells. We then assessed cancer stem cell (CSC) characteristics of both KO & control cell lines. Mammosphere formation was reduced by over 60% in KO cells. Stem cell phenotype assessed by ALDH1 & CD44+/CD24 low using FACS analysis were significantly reduced by over 30% in KO cells. Cell morphology analysis showed a shift from a mesenchymal phenotype towards an epithelial phenotype. Overall our data show that PTHrP regulates TNBC towards a more aggressive phenotype & suggest that it could be targeted therapeutically. Citation Format: Jiarong Li, Louis Doré-Savard, Karine Sellin, Anne Camirand, Richard Kremer. Ablation of parathyroid hormone-related protein in the triple negative human breast cancer line MDA-MB-231 inhibits its cancer stem cell phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3062.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".