학술논문
Tumor vessel co-option probed by single-cell analysis
Document Type
article
Author
Laure-Anne Teuwen; Laura P.M.H. De Rooij; Anne Cuypers; Katerina Rohlenova; Sébastien J. Dumas; Melissa García-Caballero; Elda Meta; Jacob Amersfoort; Federico Taverna; Lisa M. Becker; Nuphar Veiga; Anna Rita Cantelmo; Vincent Geldhof; Nadine V. Conchinha; Joanna Kalucka; Lucas Treps; Lena-Christin Conradi; Shawez Khan; Tobias K. Karakach; Stefaan Soenen; Stefan Vinckier; Luc Schoonjans; Guy Eelen; Steven Van Laere; Mieke Dewerchin; Luc Dirix; Massimiliano Mazzone; Yonglun Luo; Peter Vermeulen; Peter Carmeliet
Source
Cell Reports, Vol 35, Iss 11, Pp 109253- (2021)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: Tumor vessel co-option is poorly understood, yet it is a resistance mechanism against anti-angiogenic therapy (AAT). The heterogeneity of co-opted endothelial cells (ECs) and pericytes, co-opting cancer and myeloid cells in tumors growing via vessel co-option, has not been investigated at the single-cell level. Here, we use a murine AAT-resistant lung tumor model, in which VEGF-targeting induces vessel co-option for continued growth. Single-cell RNA sequencing (scRNA-seq) of 31,964 cells reveals, unexpectedly, a largely similar transcriptome of co-opted tumor ECs (TECs) and pericytes as their healthy counterparts. Notably, we identify cell types that might contribute to vessel co-option, i.e., an invasive cancer-cell subtype, possibly assisted by a matrix-remodeling macrophage population, and another M1-like macrophage subtype, possibly involved in keeping or rendering vascular cells quiescent.