An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates

Publication date: 13 January 2020Source: Cancer Cell, Volume 37, Issue 1Author(s): Jermaine Goveia, Katerina Rohlenova, Federico Taverna, Lucas Treps, Lena-Christin Conradi, Andreas Pircher, Vincent Geldhof, Laura P.M.H. de Rooij, Joanna Kalucka, Liliana Sokol, Melissa García-Caballero, Yingfeng Zheng, Junbin Qian, Laure-Anne Teuwen, Shawez Khan, Bram Boeckx, Els Wauters, Herbert Decaluwé, Paul De Leyn, Johan VansteenkisteSummaryHeterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single-cell RNA (scRNA)-sequenced 56,771 endothelial cells from human/mouse (peri)-tumoral lung and cultured human lung TECs, and detected 17 known and 16 previously unrecognized phenotypes, including TECs putatively regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a putative basement-membrane remodeling breach phenotype. Tip TEC signatures correlated with patient survival, and tip/breach TECs were most sensitive to vascular endothelial growth factor blockade. Only tip TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-sequenced data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen modification as a candidate angiogenic pathway.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research