MDA-MB-231 Breast Cancer Cells Resistant to Pleurocidin-Family Lytic Peptides Are Chemosensitive and Exhibit Reduced Tumor-Forming Capacity
Bibliographic record
Abstract
Direct-acting anticancer (DAA) peptides are cytolytic peptides that show promise as novel anticancer agents. DAA peptides bind to anionic molecules that are abundant on cancer cells relative to normal healthy cells, which results in preferential killing of cancer cells. Due to the mechanism by which DAA peptides kill cancer cells, it was thought that resistance would be difficult to achieve. Here, we describe the generation and characterization of two MDA-MB-231 breast cancer cell-line variants with reduced susceptibility to pleurocidin-family and mastoparan DAA peptides. Peptide resistance correlated with deficiencies in peptide binding to cell-surface structures, suggesting that resistance was due to altered composition of the cell membrane. Peptide-resistant MDA-MB-231 cells were phenotypically distinct yet remained susceptible to chemotherapy. Surprisingly, neither of the peptide-resistant breast cancer cell lines was able to establish tumors in immune-deficient mice. Histological analysis and RNA sequencing suggested that tumorigenicity was impacted by alternations in angiogenesis and extracellular matrix composition in the peptide-resistant MDA-MB-231 variants. Collectively, these data further support the therapeutic potential of DAA peptides as adjunctive treatments for cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".