Abstract 5117: Investigating the role of secreted plasminogen receptors in the establishment of the pre-metastatic breast cancer niche
Bibliographic record
Abstract
Abstract Introduction: Breast cancer is the most common cancer in women, with 25% of patients presentingsecondary tumors at diagnosis. Metastasis, responsible for over 90% of cancer deaths, involves cancer cellsescaping the primary tumor to colonize distant organs. This process requires the preparation of target sites, known as premetastatic niches (PMNs). PMNs undergo structural remodeling facilitated by cancer cell-secreted factors, including the protease plasmin (Pm), which aids in cancer cell escape by degrading tissuebarriers. Cancer cells utilize plasminogen receptors (PgRs) to convert the blood protein plasminogen (Plg)into Pm. Our research has shown that conditioned media (CM) from breast cancer cells can activate Plg toPm, suggesting the presence of PgRs in these secretions. While cell surface PgRs are established in tumorprogression, the roles of secreted PgRs within the breast cancer secretome remains undefined. Additionally, the involvement of the Plg/Pm system in PMN modulation is unexplored. We have found that CM frommalignant BCCs has higher Pm-activating potential than from non-malignant BCCs. Protein purification ofCM identified several soluble PgR-active fractions, with phosphoglycerate kinase-1 (PGK-1) emerging asa key PgR candidate. Methods: CM was isolated from highly and weakly metastatic BCC lines (MDA MB 231 vs. MCF7 & 4T1vs. 67NR). Soluble proteins were separated by size- and charge-chromatography, and fractions wereassayed for PgR activity, measured through their ability to stimulate tPA-dependent Plg-to-Pm conversion.Active fractions were pooled and identified via mass spectrometry. Results: CM from MDA MB 231 and 4T1 cells exhibited higher PgR activity and distinct chromatographicprofiles compared to MCF7 and 67NR cells. Size-exclusion chromatography revealed multiple PgR activitypeaks. Mass spectrometry identified novel PgR candidates, including glycolytic enzymes and extracellularmatrix components, PGK-1, a glycolytic enzyme, was identified in a PgR activity peak, with recombinantPGK-1 showing significant in vitro Pm generation, confirming its PgR role. Conclusions: PGK-1 is secreted by breast cancer cells and has Pm-generating potential. Futureexperiments will validate PGK-1 and other proteins as PgRs and clarify their roles in metastasis. Citation Format: Gillian Okura. Investigating the role of secreted plasminogen receptors in the establishment of the pre-metastatic breast cancer niche [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5117.
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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) | 0.006 | 0.002 |
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".