Endothelial Notch1 Activity Facilitates Metastasis

Elfriede Wieland; Juan Rodriguez-Vita; Sven S. Liebler; Carolin Mogler; Iris Moll; Stefanie E. Herberich; Elisa Espinet; Esther Herpel; Amitai Menuchin; Jenny Chang-Claude; Michael Hoffmeister; Christoffer Gebhardt; Hermann Brenner; Andreas Trumpp; Christian W. Siebel; Markus Hecker; Jochen Utikal; David Sprinzak; Andreas Fischer

doi:10.1016/j.ccell.2017.01.007

Endothelial Notch1 Activity Facilitates Metastasis

Elfriede Wieland, Juan Rodriguez-Vita, Sven S. Liebler, Carolin Mogler, Iris Moll, Stefanie E. Herberich, Elisa Espinet, Esther Herpel, Amitai Menuchin, Jenny Chang-Claude, Michael Hoffmeister, Christoffer Gebhardt, Hermann Brenner, Andreas Trumpp, Christian W. Siebel, Markus Hecker, Jochen Utikal, David Sprinzak, Andreas Fischer^*

^*Corresponding author for this work

Biochemistry Molecular Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis. Thus, sustained vascular Notch signaling facilitates metastasis by generating a senescent, pro-inflammatory endothelium. Consequently, treatment with Notch1 or VCAM1-blocking antibodies prevented Notch-driven metastasis, and genetic ablation of EC Notch signaling inhibited peritoneal neutrophil infiltration in an ovarian carcinoma mouse model.

Original language	English
Pages (from-to)	355-367
Number of pages	13
Journal	Cancer Cell
Volume	31
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2017.01.007
State	Published - 13 Mar 2017

Keywords

Notch signaling
angiogenesis
endothelial cell
extravasation
intravasation
metastasis
mouse models
neutrophils
senescence
vascular biology

UN SDGs

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

Access to Document

10.1016/j.ccell.2017.01.007

Cite this

Wieland, E., Rodriguez-Vita, J., Liebler, S. S., Mogler, C., Moll, I., Herberich, S. E., Espinet, E., Herpel, E., Menuchin, A., Chang-Claude, J., Hoffmeister, M., Gebhardt, C., Brenner, H., Trumpp, A., Siebel, C. W., Hecker, M., Utikal, J., Sprinzak, D., & Fischer, A. (2017). Endothelial Notch1 Activity Facilitates Metastasis. Cancer Cell, 31(3), 355-367. https://doi.org/10.1016/j.ccell.2017.01.007

@article{94f88d4532c84a7287cbad5f8cd404a7,

title = "Endothelial Notch1 Activity Facilitates Metastasis",

abstract = "Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis. Thus, sustained vascular Notch signaling facilitates metastasis by generating a senescent, pro-inflammatory endothelium. Consequently, treatment with Notch1 or VCAM1-blocking antibodies prevented Notch-driven metastasis, and genetic ablation of EC Notch signaling inhibited peritoneal neutrophil infiltration in an ovarian carcinoma mouse model.",

keywords = "Notch signaling, angiogenesis, endothelial cell, extravasation, intravasation, metastasis, mouse models, neutrophils, senescence, vascular biology",

author = "Elfriede Wieland and Juan Rodriguez-Vita and Liebler, {Sven S.} and Carolin Mogler and Iris Moll and Herberich, {Stefanie E.} and Elisa Espinet and Esther Herpel and Amitai Menuchin and Jenny Chang-Claude and Michael Hoffmeister and Christoffer Gebhardt and Hermann Brenner and Andreas Trumpp and Siebel, {Christian W.} and Markus Hecker and Jochen Utikal and David Sprinzak and Andreas Fischer",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = mar,

day = "13",

doi = "10.1016/j.ccell.2017.01.007",

language = "אנגלית",

volume = "31",

pages = "355--367",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "3",

}

Wieland, E, Rodriguez-Vita, J, Liebler, SS, Mogler, C, Moll, I, Herberich, SE, Espinet, E, Herpel, E, Menuchin, A, Chang-Claude, J, Hoffmeister, M, Gebhardt, C, Brenner, H, Trumpp, A, Siebel, CW, Hecker, M, Utikal, J, Sprinzak, D & Fischer, A 2017, 'Endothelial Notch1 Activity Facilitates Metastasis', Cancer Cell, vol. 31, no. 3, pp. 355-367. https://doi.org/10.1016/j.ccell.2017.01.007

TY - JOUR

T1 - Endothelial Notch1 Activity Facilitates Metastasis

AU - Wieland, Elfriede

AU - Rodriguez-Vita, Juan

AU - Liebler, Sven S.

AU - Mogler, Carolin

AU - Moll, Iris

AU - Herberich, Stefanie E.

AU - Espinet, Elisa

AU - Herpel, Esther

AU - Menuchin, Amitai

AU - Chang-Claude, Jenny

AU - Hoffmeister, Michael

AU - Gebhardt, Christoffer

AU - Brenner, Hermann

AU - Trumpp, Andreas

AU - Siebel, Christian W.

AU - Hecker, Markus

AU - Utikal, Jochen

AU - Sprinzak, David

AU - Fischer, Andreas

PY - 2017/3/13

Y1 - 2017/3/13

N2 - Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis. Thus, sustained vascular Notch signaling facilitates metastasis by generating a senescent, pro-inflammatory endothelium. Consequently, treatment with Notch1 or VCAM1-blocking antibodies prevented Notch-driven metastasis, and genetic ablation of EC Notch signaling inhibited peritoneal neutrophil infiltration in an ovarian carcinoma mouse model.

AB - Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis. Thus, sustained vascular Notch signaling facilitates metastasis by generating a senescent, pro-inflammatory endothelium. Consequently, treatment with Notch1 or VCAM1-blocking antibodies prevented Notch-driven metastasis, and genetic ablation of EC Notch signaling inhibited peritoneal neutrophil infiltration in an ovarian carcinoma mouse model.

KW - Notch signaling

KW - angiogenesis

KW - endothelial cell

KW - extravasation

KW - intravasation

KW - metastasis

KW - mouse models

KW - neutrophils

KW - senescence

KW - vascular biology

UR - http://www.scopus.com/inward/record.url?scp=85013625323&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2017.01.007

DO - 10.1016/j.ccell.2017.01.007

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:85013625323

SN - 1535-6108

VL - 31

SP - 355

EP - 367

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Endothelial Notch1 Activity Facilitates Metastasis

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this