Abstract 396: Plasticity Of The Tumor Vasculature Is Induced By Tumor Cells Via Cell Surface Receptor Tetherin

• DOI: 10.1161/atvb.43.suppl_1.396
• Publication Date: 2023-10-02T14:09:33Z
• Authors: Caitlin Bell; Sharika Bamezais; Wei Feng Ma; Nicolas Gabriel L...; Richard Baylis; Lingfeng Luo; Clint L Miller; Nicholas Leeper
• Keywords: Tetherin; Cell type

It is increasingly clear that cardiovascular disease and cancer have shared pathophysiological mechanisms beyond traditional risk factors. Murine models demonstrated tumors grow more quickly in the presence of abnormalities, targeting signaling pathways has proven efficacious both diseases. unknown, however, if smooth muscle cell (SMC) plasticity as seen atherogenesis represents yet another biologic parallel. Our aim was to understand SMC occurs tumor vasculature, how those transitions are induced. Syngeneic lines were implanted on flanks lineage-traced mice allowed for 11 days. Fluorescent microscopy revealed a population SMCs moved away from angiogenic vessels lost canonical markers. We used single RNA sequencing characterize vivo transcriptional phenotype within tumor. Principal component analysis distinct populations, with pseudotime suggesting contractile towards macrophage-like state. CellChat ligand-receptor leveraged examine differential interactions between cells classic macrophages versus SMCs. The only unique interaction surface receptors Tetherin paired immunoglobulin-like receptor A2 (PIRA2) In vitro murine treated recombinant decreased markers increased macrophage by qPCR. Exposure also overall proliferative rate, migratory capacity, phagocytic ability compared untreated knockdown PIRA2 abrogates these apparent effects Tetherin. findings demonstrate like atherogenesis, significant degrees plasticity. One phenotypic changes studies suggest sufficient induce this switching. Ongoing will establish whether inhibition Tetherin-PIRA2 axis decreases vascular