1274 Targeting tumour vascularisation through endothelial-specific Sox9 deletion reduces melanoma metastasis

The formation of de novo vascular structures is vital for melanoma growth and metastasis. Sox9 a transcription factor that highly upregulated in situations EndMT such as wound fibrosis or atherosclerosis well progenitors the endothelium (EVPs), playing crucial role stem cell self-renewal quiescence. In this study, we aimed to explore deletion on tumor vascularisation, metastasis, gene expression. Firstly, demonstrated thatSox9 expression was endothelial cells mice harboring melanomas. Similarly, induced overexpression SOX9 human whether co-culture conditioned medium. Endothelial-specific conditional knockout (Sox9fl/fl/Cdh5CreERt2/Rosa-YFP) resulted significant reduction total B16-F0 HcMel12 tumors inoculated subcutaneously. Immunofluorescence staining sections confirmed number area CD31+ vessels but revealed increase pericyte coverage suggesting increased maturity remaining upon from endothelium. shRNA knockdown inhibited tube migration vitro. These changes translated into hypoxia by GLUT1 glycolysis shown RNAseq. Spatial transcriptomics with endothelial-specific versus controls showed cell-cell interactions. Moreover, there lung metastases after summary, fewer more mature centre reduced metastatic dissemination, strategies target pathway may restore normal function blood prevent disease progression.