Abstract 3277: The Fps/Fes protein-tyrosine kinase serves a stromal tissue-specific supporting role in an orthotopic mouse model of breast cancer
Bibliographic record
Abstract
Abstract Fes (also known as Fps) is a cytoplasmic protein tyrosine kinase that is highly expressed in breast epithelial cells during lactation, as well as in vascular endothelial and myeloid cells. Retrovirally encoded oncogenic alleles of Fps/Fes are associated with tumors in chickens and cats and cause tumors in transgenic mice; however, a role for Fes in human cancer has not been established. We hypothesized that Fes promotes breast tumorigenesis through tumor cell intrinsic functions as well as through functions in stromal tissues including vascular endothelial cells and macrophages. To test the potential tumor cell intrinsic role, AC2M2 cells, a highly metastatic mouse mammary carcinoma cell line, were transduced with expression plasmids encoding wild-type, kinase-inactivated or activated Fes. These cells were then engrafted into the mammary fat pads of nude mice and tumorigenesis was assessed by ultrasound (longitudinal tumor volume measurement), Doppler (tumor-associated vascular flow) and biophotonic imaging of GFP-expressing tumor cells (lung metastasis). There was no obvious difference in tumor growth and angiogenesis at the orthotopic site between each cell line and no apparent difference in lung metastasis. To test the potential stromal role of Fes in breast tumorigenesis, parental AC2M2 cells were injected into the mammary fat pads of wild type and Fes-null nude mice, and tumorigenesis and metastasis were assessed as described above. Wild type mice developed tumors significantly faster than Fes-null mice and there was earlier tumor neovascularization and more recruitment of macrophages. There was also a significantly higher degree of lung metastasis in wild type vs Fes-null mice. These observations are consistent with a tumor promoting role for Fes acting at the level of the vascular endothelium and macrophages. This might include promoting early tumor neovasularization through direct roles in vascular endothelial cells as well as indirect roles associated with macrophages. The increased metastatic potential also suggests roles in both these cell lineages. This provides genetic evidence that the Fes protein-tyrosine kinase represents a potential novel therapeutic target in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3277.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".