Tumor vessel co-option probed by single-cell analysis

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 SoenenStefan Vinckier, Luc Schoonjans, Guy Eelen, Steven Van Laere, Mieke Dewerchin, Luc Dirix, Massimiliano Mazzone, Yonglun Luo*, Peter Vermeulen, Peter Carmeliet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number109253
JournalCell Reports
Issue number11
StatePublished - 15 Jun 2021
Externally publishedYes


  • anti-angiogenic therapy
  • cancer cells
  • endothelial cells
  • macrophages
  • metastasis
  • pericytes
  • resistance
  • single-cell RNA sequencing
  • tumor angiogenesis
  • tumor vessel co-option


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