Monocyte Induction of E-Selectin-Mediated Endothelial
Activation Releases VE-Cadherin Junctions to Promote Tumor Cell
Extravasation in the Metastasis Cascade

J 2016

Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade

HAUSELMANN, Irina, Marko ROBLEK, Darya PROTSYUK, Volker HUCK, Lucia KNOPFOVÁ et. al.

Basic information

Original name

Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade

Authors

HAUSELMANN, Irina (756 Switzerland), Marko ROBLEK (40 Austria), Darya PROTSYUK (756 Switzerland), Volker HUCK (276 Germany), Lucia KNOPFOVÁ (203 Czech Republic, belonging to the institution), Sandra GRASSLE (276 Germany), Alexander T. BAUER (276 Germany), Stefan W. SCHNEIDER (276 Germany) and Lubor BORSIG (703 Slovakia)

Edition

Cancer Research, USA, American Association for Cancer Research, 2016, 0008-5472

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 9.122

RIV identification code

RIV/00216224:14310/16:00094259

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1158/0008-5472.CAN-16-0784

UT WoS

000383358300013

Keywords in English

VASCULAR ENDOTHELIUM; PROTEIN-KINASE; CANCER-CELLS; TRANSENDOTHELIAL MIGRATION; ADHESION MOLECULES; LIVER METASTASIS; P-SELECTIN; EXPRESSION; RECRUITMENT; GROWTH

Abstract

V originále

Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin-dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. (C) 2016 AACR.

Citovat

HAUSELMANN, Irina, Marko ROBLEK, Darya PROTSYUK, Volker HUCK, Lucia KNOPFOVÁ, Sandra GRASSLE, Alexander T. BAUER, Stefan W. SCHNEIDER and Lubor BORSIG. Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade. Cancer Research. USA: American Association for Cancer Research, 2016, vol. 76, No 18, p. 5302-5312. ISSN 0008-5472. Available from: https://dx.doi.org/10.1158/0008-5472.CAN-16-0784.

@article{1380329,
   author = {Hauselmann, Irina and Roblek, Marko and Protsyuk, Darya and Huck, Volker and Knopfová, Lucia and Grassle, Sandra and Bauer, Alexander T. and Schneider, Stefan W. and Borsig, Lubor},
   article_location = {USA},
   article_number = {18},
   doi = {http://dx.doi.org/10.1158/0008-5472.CAN-16-0784},
   keywords = {VASCULAR ENDOTHELIUM; PROTEIN-KINASE; CANCER-CELLS; TRANSENDOTHELIAL MIGRATION; ADHESION MOLECULES; LIVER METASTASIS; P-SELECTIN; EXPRESSION; RECRUITMENT; GROWTH},
   language = {eng},
   issn = {0008-5472},
   journal = {Cancer Research},
   title = {Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade},
   volume = {76},
   year = {2016}
}

TY  - JOUR
ID  - 1380329
AU  - Hauselmann, Irina - Roblek, Marko - Protsyuk, Darya - Huck, Volker - Knopfová, Lucia - Grassle, Sandra - Bauer, Alexander T. - Schneider, Stefan W. - Borsig, Lubor
PY  - 2016
TI  - Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade
JF  - Cancer Research
VL  - 76
IS  - 18
SP  - 5302-5312
EP  - 5302-5312
PB  - American Association for Cancer Research
SN  - 00085472
KW  - VASCULAR ENDOTHELIUM
KW  - PROTEIN-KINASE
KW  - CANCER-CELLS
KW  - TRANSENDOTHELIAL MIGRATION
KW  - ADHESION MOLECULES
KW  - LIVER METASTASIS
KW  - P-SELECTIN
KW  - EXPRESSION
KW  - RECRUITMENT
KW  - GROWTH
N2  - Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin-dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. (C) 2016 AACR.
ER  -

HAUSELMANN, Irina, Marko ROBLEK, Darya PROTSYUK, Volker HUCK, Lucia KNOPFOVÁ, Sandra GRASSLE, Alexander T. BAUER, Stefan W. SCHNEIDER and Lubor BORSIG. Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade. \textit{Cancer Research}. USA: American Association for Cancer Research, 2016, vol.~76, No~18, p.~5302-5312. ISSN~0008-5472. Available from: https://dx.doi.org/10.1158/0008-5472.CAN-16-0784.

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