IL17A-Mediated Endothelial Breach Promotes Metastasis Formation
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IL17A-Mediated Endothelial Breach Promotes Metastasis Formation. / Kulig, Paulina; Burkhard, Sara; Mikita-Geoffroy, Joanna; Croxford, Andrew L; Hövelmeyer, Nadine; Gyülvészi, Gabor; Gorzelanny, Christian; Waisman, Ari; Borsig, Lubor; Becher, Burkhard.
in: CANCER IMMUNOL RES, Jahrgang 4, Nr. 1, 01.2016, S. 26-32.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - IL17A-Mediated Endothelial Breach Promotes Metastasis Formation
AU - Kulig, Paulina
AU - Burkhard, Sara
AU - Mikita-Geoffroy, Joanna
AU - Croxford, Andrew L
AU - Hövelmeyer, Nadine
AU - Gyülvészi, Gabor
AU - Gorzelanny, Christian
AU - Waisman, Ari
AU - Borsig, Lubor
AU - Becher, Burkhard
N1 - ©2015 American Association for Cancer Research.
PY - 2016/1
Y1 - 2016/1
N2 - The role of the IL23/IL17A axis in tumor-immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a(-/-) mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression of E-selectin and VCAM-1 by lung endothelial cells in vivo. In transgenic mice, specific targeting of IL17A to the endothelium increased the number of tumor foci. Moreover, the direct impact of IL17A on lung endothelial cells resulted in impaired endothelial barrier integrity, showing that IL17A promotes the formation of lung metastases through tumor-endothelial transmigration.
AB - The role of the IL23/IL17A axis in tumor-immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a(-/-) mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression of E-selectin and VCAM-1 by lung endothelial cells in vivo. In transgenic mice, specific targeting of IL17A to the endothelium increased the number of tumor foci. Moreover, the direct impact of IL17A on lung endothelial cells resulted in impaired endothelial barrier integrity, showing that IL17A promotes the formation of lung metastases through tumor-endothelial transmigration.
KW - Animals
KW - Capillary Permeability
KW - Carcinoma, Lewis Lung
KW - Cell Adhesion
KW - Cell Line, Tumor
KW - Endothelial Cells
KW - Endothelium, Vascular
KW - Interleukin-17
KW - Lung Neoplasms
KW - Melanoma, Experimental
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Neoplasm Transplantation
KW - Transendothelial and Transepithelial Migration
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1158/2326-6066.CIR-15-0154
DO - 10.1158/2326-6066.CIR-15-0154
M3 - SCORING: Journal article
C2 - 26586773
VL - 4
SP - 26
EP - 32
JO - CANCER IMMUNOL RES
JF - CANCER IMMUNOL RES
SN - 2326-6066
IS - 1
ER -