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
Affiliations
Lucile Massenet-Regad
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France; Université Paris-Saclay, F-91190 Saint Aubin, France; Corresponding author
Justine Poirot
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France; Université Paris-Saclay, F-91190 Saint Aubin, France
Margaret Jackson
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France
Caroline Hoffmann
INSERM U932, Department of Surgical Oncology, PSL University, Institut Curie, 75005 Paris, France; Owkin France, 75010 Paris, France
Elise Amblard
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France; CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Grenoble Alpes University, 38000 Grenoble, France
Fanny Onodi
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France
Fatiha Bouhidel
Department of Pathology, Saint-Louis Hospital, AP-HP.Nord, Université Paris Cité, 75010 Paris, France
Malika Djouadou
Department of Urology, Saint-Louis Hospital, AP-HP.Nord, Université Paris Cité, 75010 Paris, France
Idir Ouzaid
Department of Urology, Bichat-Claude Bernard Hospital, AP-HP.Nord, Université Paris Cité, 75018 Paris, France
Evanguelos Xylinas
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France; Department of Urology, Bichat-Claude Bernard Hospital, AP-HP.Nord, Université Paris Cité, 75018 Paris, France
Jasna Medvedovic
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France
Vassili Soumelis
Université Paris Cité, INSERM, U976 HIPI, F-75010 Paris, France; Owkin France, 75010 Paris, France; Department of Immunology-Histocompatibility, Saint-Louis Hospital, AP-HP.Nord, Université Paris Cité, 75010 Paris, France; Corresponding author
Summary: 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.
