OP01 Prion-like protein doppel as a novel marker for tumoral angiogenesis and tumor targeting

نویسندگان

چکیده

Approved angiogenesis inhibitors generally target certain growth factors or their receptors, which exist in both normal and cancerous cells; this results suppression of cell-signaling pathways throughout the body causes adverse effects. For reason, there is a need for new inhibitor that can specifically tumor vasculature. In our previous study, we revealed doppel, prion-like protein, was overexpressed vasculatures, but not endothelium, its expression enhanced blood vessel formation. Doppel monoclonal antibodies were produced through 2-track methods. We evaluated whether doppel antibody inhibits by spheroid assays immunoblotting. Using hanging drop method, human colonic tumor-associated endothelial cells (HCTECs) spheroids embedded incubated with factor antibodies. Further, conducted immunoblot microarray investigating underlying mechanisms. addition, injected fluorescent dye-conjugated into xenograft mouse models visualized tumor-targeting efficacy using vivo imaging system (IVIS). Also, effect internalization tumoral confocal microscopy. assays, found sprouting. anti- phosphorylation amount phosphorylated VEGFR2 decreased antibody-treated groups. When lysate added to kit, STAT5A beta-catenin inhibited. Inhibition may promote apoptosis increase sensitivity anticancer drugs, inhibition further angiogenesis. accumulates tumor. cancer cells, targets then occurs. development have been screened selected anti-angiogenic efficacy. validated hypothesis showing inhibit angiogenesis-related factors, turn brings also confirmed novel target, could be marker targeting. hope expected superior vasculature-specific overcome limitations existing agents.

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ژورنال

عنوان ژورنال: ESMO open

سال: 2022

ISSN: ['2059-7029']

DOI: https://doi.org/10.1016/j.esmoop.2022.100674