Anti-Tumor Effects of Semaphorin 4D Blockade Unravel a Novel Pro-Invasive Mechanism of Vascular Targeting Agents

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Introduction: One of the main consequences of inhibition of neovessel growth produced by angiogenesis inhibitors is increased intratumor hypoxia. Growing evidence indicates that tumor cells escape from this hypoxic environment to better nourished locations, presenting hypoxia as a positive stimulus for invasion. Particularly, anti-VEGF/R therapies produce hypoxia-induced invasion and metastasis in a spontaneous mouse model of pancreatic neuroendocrine cancer, RIP1-Tag2.

Aim(s): In search for alternative angiogenesis targets to be blocked in neuroendocrine tumors (NETs), we focused our attention to Semaphorin 4D (Sema4D) as a well-established pro-angiogenic molecule.

Materials and methods: A novel vascular targeting agent blocking Sema4D (Mab67 anti-Sema4D Ab, Vaccinex Inc.) was used to treat RIP1-Tag2 NETs transgenic mice at 1mg/animal/week.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Casanovas O

Authors: Zuazo-Gaztelu I, Pàez-Ribes M, Carrasco P, Martín-Mitjana L, Sallaberry J,

Keywords: Antiangiogenic therapies, Semaphorin 4D, Mouse models of NETs, Invasion and metastasis,