Unknown

Dataset Information

0

Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody


ABSTRACT: The Angiopoietin (Ang)-Tie pathway has been intensely pursued as candidate second generation anti-angiogenic target. While much of the translational work has focused on the ligand Ang2, the clinical efficacy of Ang2-targeting drugs is limited and failed to improve patient survival. In turn, the orphan receptor Tie1 remains therapeutically unexplored, although its endothelial-specific genetic deletion has previously been shown to result in a strong reduction in metastatic growth. Here, we report a novel Tie1 function-blocking antibody (AB-Tie1-39), which suppressed postnatal retinal angiogenesis. During primary tumor growth, neoadjuvant administration of AB-Tie1-39 strongly impeded systemic metastasis. Furthermore, administration of AB-Tie1-39 in a perioperative therapeutic window led to a significant survival advantage as compared to control-IgG-treated mice. Additional in vivo experimental metastasis and in vitro transmigration assays concurrently revealed that AB-Tie1-39 treatment suppressed tumor cell extravasation at secondary sites. Taken together, the data phenocopy previous genetic work in endothelial Tie1 KO mice and thereby validate AB-Tie1-39 as a Tie1 function-blocking antibody. The study establishes Tie1 as a therapeutic target for metastasis in a perioperative or neoadjuvant setting.

SUBMITTER: Dr. Mahak Singhal 

PROVIDER: S-SCDT-EMM-2019-11164 | biostudies-other |

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC7278563 | biostudies-literature
| S-EPMC4344398 | biostudies-literature
| S-EPMC3540950 | biostudies-literature
| S-EPMC10017418 | biostudies-literature
2011-12-23 | E-GEOD-34666 | biostudies-arrayexpress
| S-EPMC5356841 | biostudies-literature
| S-EPMC9027532 | biostudies-literature
| S-EPMC4120074 | biostudies-literature
| S-EPMC3309130 | biostudies-literature
2011-12-23 | GSE34666 | GEO