Michael IP Orebrand M Lima M Pereira B Volpert O Quaggin SE Jeansson M 2017 BACKGROUND Angipoietin-1 activation of the tyrosine kinase receptor Tek expressed mainly on endothelial cells leads to survival and stabilization of endothelial cells. Studies have shown that Angiopoietin-1 counteracts permeability induced by a number of stimuli. Here, we test the hypothesis that loss of Angiopoietin-1/Tek signaling in the vasculature would increase metastasis. METHODS Angiopoietin-1 was deleted in mice just before birth using floxed Angiopoietin-1 and Tek mice crossed to doxycycline-inducible bitransgenic ROSA-rtTA/tetO-Cre mice. By crossing Angiopoietin-1 knockout mice to the MMTV-PyMT autochthonous mouse breast cancer model, we investigated primary tumor growth and metastasis to the lung. Furthermore, we utilized B16F10 melanoma cells subcutaneous and experimental lung metastasis models in Angiopoietin-1 and Tek knockout mice. RESULTS We found that primary tumor growth in MMTV-PyMT mice was unaffected, while metastasis to the lung was significantly increased in Angiopoietin-1 knockout MMTV-PyMT mice. In addition, angiopoietin-1 deficient mice exhibited a significant increase in lung metastasis of B16F10 melanoma cells, compared to wild type mice 3 weeks after injection. Additional experiments showed that this was likely an early event due to increased attachment or extravasation of tumor cells, since seeding of tumor cells was significantly increased 4 and 24 h post tail vein injection. Finally, using inducible Tek knockout mice, we showed a significant increase in tumor cell seeding to the lung, suggesting that Angiopoietin-1/Tek signaling is important for vascular integrity to limit metastasis. CONCLUSIONS This study show that loss of the Angiopoietin-1/Tek vascular growth factor system leads to increased metastasis without affecting primary tumor growth. https://sonar.ch/global/documents/105110 eng info:eu-repo/semantics/altIdentifier/doi/10.1186/s12885-017-3531-y info:eu-repo/semantics/altIdentifier/pmid/28800750 BMC cancer. - 2017 Angiopoietin-1 B16F10 melanoma MMTV-PyMT Metastasis Angiopoietin-1 Animals Female Gene Expression Lung Neoplasms Male Mammary Neoplasms, Experimental Melanoma Mice Mice, Knockout Neoplasm Metastasis Signal Transduction Angiopoietin-1 deficiency increases tumor metastasis in mice. http://purl.org/coar/resource_type/c_6501