<i>Bmpr2</i> Loss in the Vascular Endothelium Enhances Neoangiogenesis and Growth of Lung Metastatic Lesions in a Mouse Model of Breast Cancer
Bibliographic record
Abstract
ABSTRACT Bone morphogenetic protein‐9 (BMP9) has been implicated as a regulator of metastasis and tumor angiogenesis, with contrasting studies demonstrating both pro‐ and antiangiogenic roles for BMP9 across different cancer cell lines and animal models. However, these works have yet to define the contribution of the type‐II BMP receptor (BMPR‐II) to these processes, or assess whether the effects of BMP9 are mediated via actions on the endothelium, the tumor, or its microenvironment. Here, we demonstrate that the heterozygous ( Bmpr2 EC+/− ) or homozygous ( Bmpr2 EC−/− ) deletion of BMPR‐II in the pulmonary endothelium is associated with increased overall burden and vascularization of metastases in the lungs of mice subjected to the EO771 orthotopic engraftment model of metastatic breast cancer. These increases, relative to Bmpr2 EC+/+ littermates, were observed despite equivalent primary mammary tumor growth across mice of all genotypes. In vitro , secreted factors or extracellular matrix components from BMPR‐II‐silenced human pulmonary arterial endothelial cells (HPAECs) did not alter EO771 proliferation relative to controls. However, endothelial BMPR‐II depletion did eliminate the capacity of BMP9 to suppress both HPAEC migration to VEGF 165 and EO771 transmigration across an HPAEC monolayer. In a tail vein injection model, the short‐term establishment of EO771 cell metastatic lesions was equivalent in the lungs of female Bmpr2 EC+/− and Bmpr2 EC−/− mice, relative to Bmpr2 EC+/+ controls, suggesting that the enhanced lung tumor burden observed in orthotopically implanted mice with endothelial Bmpr2 deletion is likely a consequence of enhanced tumor vascularization, rather than altered lung retention and engraftment. Our findings identify an important role for endothelial BMPR‐II signaling in regulating the vascularization of metastatic lesions in the lungs.
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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".