IL17A-Mediated Endothelial Breach Promotes Metastasis Formation

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 -