Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma

大规模细胞间通讯分析揭示了透明细胞肾细胞癌中血管生成素依赖性肿瘤进展

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作者:Lucile Massenet-Regad ,Justine Poirot ,Margaret Jackson ,Caroline Hoffmann ,Elise Amblard ,Fanny Onodi ,Fatiha Bouhidel ,Malika Djouadou ,Idir Ouzaid ,Evanguelos Xylinas ,Jasna Medvedovic ,Vassili Soumelis

Abstract

Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.

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