Tyrosine Phosphatase PTPRJ/DEP-1 Is an Essential Promoter of Vascular Permeability, Angiogenesis, and Tumor Progression
Bibliographic record
Abstract
The protein tyrosine phosphatase PTPRJ/DEP-1 has been implicated in negative growth regulation in endothelial cells, where its expression varies at transitions between proliferation and contact inhibition. However, in the same cells, DEP-1 has also been implicated in VEGF-dependent Src activation, permeability, and capillary formation, suggesting a positive role in regulating these functions. To resolve this dichotomy in vivo, we investigated postnatal angiogenesis and vascular permeability in a DEP-1-deficient mouse. In this study, we report that DEP-1 is required for Src activation and phosphorylation of its endothelial cell-specific substrate, VE-cadherin, after systemic injection of VEGF. Accordingly, VEGF-induced vascular leakage was abrogated in the DEP-1-deficient mice. Furthermore, capillary formation was impaired in murine aortic tissue rings or Matrigel plugs infused with VEGF. In the absence of DEP-1, angiogenesis triggered by ischemia or during tumor formation was defective, which in the latter case was associated with reduced tumor cell proliferation and increased apoptosis. Macrophage infiltration was also impaired, reflecting reduced vascular permeability in the tumors or a possible cell autonomous effect of DEP-1. Consequently, the formation of spontaneous and experimental lung metastases was strongly decreased in DEP-1-deficient mice. In clinical specimens of cancer, less vascularized tumors exhibited lower microvascular expression of DEP-1. Altogether, our results established DEP-1 as an essential driver of VEGF-dependent permeability, angiogenesis, and metastasis, suggesting a novel therapeutic route to cancer treatment. Cancer Res; 76(17); 5080-91. ©2016 AACR.
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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 | 0.001 | 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 | 0.001 |
| 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".