Functional assessment of von Willebrand factor expression by cancer cells of non-endothelial origin
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
// Anahita Mojiri 1 , Konstantin Stoletov 2 , Maria Areli Lorenzana Carrillo 1 , Lian Willetts 2 , Saket Jain 2 , Roseline Godbout 2 , Paul Jurasz 3 , Consolato M. Sergi 4 , David D. Eisenstat 2, 5 , John D. Lewis 2 , Nadia Jahroudi 1 1 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada 2 Department of Oncology, University of Alberta, Edmonton, Alberta, Canada 3 Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada 4 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada 5 Departments of Medical Genetics and Pediatrics, University of Alberta, Edmonton, Alberta, Canada Correspondence to: Nadia Jahroudi, email: nadia.jahroudi@ualberta.ca Keywords: von Willebrand factor, cancer, extravasation, transcription, transcription factor Received: April 05, 2016     Accepted: November 30, 2016     Published: December 27, 2016 ABSTRACT Von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. Normally it is expressed exclusively in endothelial cells (ECs) and megakaryocytes. However, a few studies have reported VWF detection in cancer cells of non-endothelial origin, including osteosarcoma. A role for VWF in cancer metastasis has long been postulated but evidence supporting both pro- and anti-metastatic roles for VWF has been presented. We hypothesized that the role of VWF in cancer metastasis is influenced by its cellular origin and that cancer cell acquisition of VWF expression may contribute to enhanced metastatic potential. We demonstrated de novo expression of VWF in glioma as well as osteosarcoma cells. Endothelial monolayer adhesion, transmigration and extravasation capacities of VWF expressing cancer cells were shown to be enhanced compared to non-VWF expressing cells, and were significantly reduced as a result of VWF knock down. VWF expressing cancer cells were also detected in patient tumor samples of varying histologies. Analyses of the mechanism of transcriptional activation of the VWF in cancer cells demonstrated a pattern of trans-activating factor binding and epigenetic modifications consistent overall with that observed in ECs. These results demonstrate that cancer cells of non-endothelial origin can acquire de novo expression of VWF, which can enhance processes, including endothelial and platelet adhesion and extravasation, that contribute to cancer metastasis.
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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) | 0.007 | 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 it