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

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

doi:10.1016/j.isci.2023.108367

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

iScience. 2023 Oct 31;26(12):108367. doi: 10.1016/j.isci.2023.108367. eCollection 2023 Dec 15.

Authors

Lucile Massenet-Regad^{1

2}, Justine Poirot^{1

2}, Margaret Jackson¹, Caroline Hoffmann^{3

4}, Elise Amblard^{1

5}, Fanny Onodi¹, Fatiha Bouhidel⁶, Malika Djouadou⁷, Idir Ouzaid⁸, Evanguelos Xylinas^{1

8}, Jasna Medvedovic¹, Vassili Soumelis^{1

4

9}

Affiliations

¹ Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France.
² Université Paris-Saclay, F-91190 Saint Aubin, France.
³ INSERM U932, Department of Surgical Oncology, PSL University, Institut Curie, 75005 Paris, France.
⁴ Owkin France, 75010 Paris, France.
⁵ CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, 38000 Grenoble, France.
⁶ Department of Pathology, Saint-Louis Hospital, AP-HP.Nord, Université Paris Cité, 75010 Paris, France.
⁷ Department of Urology, Saint-Louis Hospital, AP-HP.Nord, Université Paris Cité, 75010 Paris, France.
⁸ Department of Urology, Bichat-Claude Bernard Hospital, AP-HP.Nord, Université Paris Cité, 75018 Paris, France.
⁹ Department of Immunology-Histocompatibility, Saint-Louis Hospital, AP-HP.Nord, Université Paris Cité, 75010 Paris, France.

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.

Keywords: Cancer; Microenvironment; Transcriptomics.

Grants and funding

WT_/Wellcome Trust/United Kingdom