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 Soenen; Stefan Vinckier; Luc Schoonjans; Guy Eelen; Steven Van Laere; Mieke Dewerchin; Luc Dirix; Massimiliano Mazzone; Yonglun Luo; Peter Vermeulen; Peter Carmeliet

doi:10.1016/j.celrep.2021.109253

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 journal › Article › peer-review

Abstract

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 language	English
Article number	109253
Journal	Cell Reports
Volume	35
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2021.109253
State	Published - 15 Jun 2021
Externally published	Yes

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2021.109253

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Teuwen, L. A., De Rooij, L. P. M. H., Cuypers, A., Rohlenova, K., Dumas, S. J., García-Caballero, M., Meta, E., Amersfoort, J., Taverna, F., Becker, L. M., Veiga, N., Cantelmo, A. R., Geldhof, V., Conchinha, N. V., Kalucka, J., Treps, L., Conradi, L. C., Khan, S., Karakach, T. K., ... Carmeliet, P. (2021). Tumor vessel co-option probed by single-cell analysis. Cell Reports, 35(11), Article 109253. https://doi.org/10.1016/j.celrep.2021.109253

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title = "Tumor vessel co-option probed by single-cell analysis",

abstract = "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.",

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

author = "Teuwen, {Laure Anne} and {De Rooij}, {Laura P.M.H.} and Anne Cuypers and Katerina Rohlenova and Dumas, {S{\'e}bastien J.} and Melissa Garc{\'i}a-Caballero and Elda Meta and Jacob Amersfoort and Federico Taverna and Becker, {Lisa M.} and Nuphar Veiga and Cantelmo, {Anna Rita} and Vincent Geldhof and Conchinha, {Nadine V.} and Joanna Kalucka and Lucas Treps and Conradi, {Lena Christin} and Shawez Khan and Karakach, {Tobias K.} and Stefaan Soenen and Stefan Vinckier and Luc Schoonjans and Guy Eelen and {Van Laere}, Steven and Mieke Dewerchin and Luc Dirix and Massimiliano Mazzone and Yonglun Luo and Peter Vermeulen and Peter Carmeliet",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = jun,

day = "15",

doi = "10.1016/j.celrep.2021.109253",

language = "אנגלית",

volume = "35",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

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Teuwen, LA, De Rooij, LPMH, Cuypers, A, Rohlenova, K, Dumas, SJ, García-Caballero, M, Meta, E, Amersfoort, J, Taverna, F, Becker, LM, Veiga, N, Cantelmo, AR, Geldhof, V, Conchinha, NV, Kalucka, J, Treps, L, Conradi, LC, Khan, S, Karakach, TK, Soenen, S, Vinckier, S, Schoonjans, L, Eelen, G, Van Laere, S, Dewerchin, M, Dirix, L, Mazzone, M, Luo, Y, Vermeulen, P & Carmeliet, P 2021, 'Tumor vessel co-option probed by single-cell analysis', Cell Reports, vol. 35, no. 11, 109253. https://doi.org/10.1016/j.celrep.2021.109253

TY - JOUR

T1 - Tumor vessel co-option probed by single-cell analysis

AU - Teuwen, Laure Anne

AU - De Rooij, Laura P.M.H.

AU - Cuypers, Anne

AU - Rohlenova, Katerina

AU - Dumas, Sébastien J.

AU - García-Caballero, Melissa

AU - Meta, Elda

AU - Amersfoort, Jacob

AU - Taverna, Federico

AU - Becker, Lisa M.

AU - Veiga, Nuphar

AU - Cantelmo, Anna Rita

AU - Geldhof, Vincent

AU - Conchinha, Nadine V.

AU - Kalucka, Joanna

AU - Treps, Lucas

AU - Conradi, Lena Christin

AU - Khan, Shawez

AU - Karakach, Tobias K.

AU - Soenen, Stefaan

AU - Vinckier, Stefan

AU - Schoonjans, Luc

AU - Eelen, Guy

AU - Van Laere, Steven

AU - Dewerchin, Mieke

AU - Dirix, Luc

AU - Mazzone, Massimiliano

AU - Luo, Yonglun

AU - Vermeulen, Peter

AU - Carmeliet, Peter

PY - 2021/6/15

Y1 - 2021/6/15

N2 - 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.

AB - 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.

KW - anti-angiogenic therapy

KW - cancer cells

KW - endothelial cells

KW - macrophages

KW - metastasis

KW - pericytes

KW - resistance

KW - single-cell RNA sequencing

KW - tumor angiogenesis

KW - tumor vessel co-option

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U2 - 10.1016/j.celrep.2021.109253

DO - 10.1016/j.celrep.2021.109253

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C2 - 34133923

AN - SCOPUS:85107954184

SN - 2211-1247

VL - 35

JO - Cell Reports

JF - Cell Reports

IS - 11

M1 - 109253

ER -

Tumor vessel co-option probed by single-cell analysis

Abstract

Keywords

UN SDGs

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