Antibody-based targeting of alternatively spliced tissue factor: a new approach to impede the primary growth and spread of pancreatic ductal adenocarcinoma
Bibliographic record
Abstract
// Dusten Unruh 1 , Betül Ünlü 2 , Clayton S. Lewis 1 , Xiaoyang Qi 1 , Zhengtao Chu 1 , Robert Sturm 1 , Ryan Keil 1 , Syed A. Ahmad 1 , Timofey Sovershaev 3 , Mariette Adam 4 , Patrick Van Dreden 4 , Barry J. Woodhams 5 , Divya Ramchandani 6 , Georg F. Weber 6 , Janusz W. Rak 7 , Alisa S. Wolberg 8 , Nigel Mackman 8 , Henri H. Versteeg 2 , Vladimir Y. Bogdanov 1 1 College of Medicine, University of Cincinnati, Cincinnati, OH, USA 2 Leiden University Medical Center, Leiden, The Netherlands 3 The Arctic University of Norway, Tromsø, Norway 4 Diagnostica Stago R & D, Gennevilliers, France 5 Haemacon Ltd, Bromley, UK 6 College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA 7 McGill University Health Centre, Montreal Children’s Hospital, Montreal, Canada 8 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Correspondence to: Vladimir Y. Bogdanov, email: vladimir.bogdanov@uc.edu Keywords: pancreatic cancer, tissue factor, alternative splicing, β1 integrins, metastasis Received: August 25, 2015 Accepted: February 13, 2016 Published: March 07, 2016 ABSTRACT Alternatively spliced Tissue Factor (asTF) is a secreted form of Tissue Factor (TF), the trigger of blood coagulation whose expression levels are heightened in several forms of solid cancer, including pancreatic ductal adenocarcinoma (PDAC). asTF binds to β1 integrins on PDAC cells, whereby it promotes tumor growth, metastatic spread, and monocyte recruitment to the stroma. In this study, we determined if targeting asTF in PDAC would significantly impact tumor progression. We here report that a novel inhibitory anti-asTF monoclonal antibody curtails experimental PDAC progression. Moreover, we show that tumor-derived asTF is able to promote PDAC primary growth and spread during early as well as later stages of the disease. This raises the likelihood that asTF may comprise a viable target in early- and late-stage PDAC. In addition, we show that TF expressed by host cells plays a significant role in PDAC spread. Together, our data demonstrate that targeting asTF in PDAC is a novel strategy to stem PDAC progression and spread.
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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".