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bioRxiv · 10.1101/2024.12.22.629954

The antiangiogenic peptide VIAN-c4551 inhibits lung melanoma metastasis in mice by reducing pulmonary vascular permeability

Perez, A. L.·Zamora, M.·Bahena, M. M.·Aramburo-Williams, R. M.·Adan-Castro, E. M.·Bertsch, T.·Triebel, J.·Martinez de la Escalera, G. M.·Robles, J. P. M.·Clapp, C.
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Abstract

IntroductionCancer cells drive the increase in vascular permeability mediating tumor cell extravasation and metastatic seeding. VIAN-c4551, an antiangiogenic peptide analog of vasoinhibin, inhibits the growth and vascularization of melanoma tumors in mice. Because VIAN-c4551 is a potent inhibitor of vascular permeability, we evaluated whether its antitumor action extended to a reduction in metastasis generation. MethodsCirculating levels of vascular endothelial growth factor (VEGF), lung vascular permeability, melanoma cell extravasation, and melanoma pulmonary nodules were assessed in C57BL/6J mice intravenously inoculated with murine melanoma B16-F10 cells after acute treatment with VIAN-c4551. VEGF levels, transendothelial electrical resistance, and transendothelial migration in cocultures of B16-F10 cells and endothelial cell monolayers supported the findings. ResultsB16-F10 cells increased circulating VEGF levels and elevated lung vascular permeability 2 hours after inoculation. VIAN-c4551 prevented enhanced vascular permeability and reduced melanoma cell extravasation after 2 hours and the number and size of macroscopic and microscopic melanoma tumors in lungs after 17 days. In vitro, VIAN-c4551 suppressed the B16-F10 cell-induced and VEGF mediated increase in endothelial cell monolayer permeability and the transendothelial migration of B16-F10 cells. ConclusionsThese findings support the inhibition of distant vascular permeability for the prevention of tumor metastasis and unveil the anti-vascular permeability factor VIAN-c4551 as a potential therapeutic drug able to prevent metastasis generation by lowering the extravasation of melanoma cells.

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Perez, A. L., Zamora, M., Bahena, M. M., Aramburo-Williams, R. M., Adan-Castro, E. M., Bertsch, T., Triebel, J., Martinez de la Escalera, G. M., Robles, J. P. M., Clapp, C.. 2024-12-22. The antiangiogenic peptide VIAN-c4551 inhibits lung melanoma metastasis in mice by reducing pulmonary vascular permeability. https://doi.org/10.1101/2024.12.22.629954

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