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Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway

Monika Julia Wolf, Alexandra Hoos, Judith Bauer, Steffen Boettcher, Markus Knust, Achim Weber, Nicole Simonavicius, Christoph Schneider, Matthias Lang and Michael Sturzl, et al. (2012) CANCER CELL. 22(1). p.91-105
abstract
Increased expression of the chemokine CCL2 in tumor cells correlates with enhanced metastasis, poor prognosis, and recruitment of CCR2(+)Ly6C(hi) monocytes. However, the mechanisms driving tumor cell extravasation through the endothelium remain elusive. Here, we describe CCL2 upregulation in metastatic UICC stage IV colon carcinomas and demonstrate that tumor cell-derived CCL2 activates the CCR2(+) endothelium to increase vascular permeability in vivo. CCR2 deficiency prevents colon carcinoma extravasation and metastasis. Of note, CCR2 expression on radio-resistant cells or endothelial CCR2 expression restores extravasation and metastasis in Ccr2(-/-) mice. Reduction of CCR2 expression on myeloid cells decreases but does not prevent metastasis. CCL2-induced vascular permeability and metastasis is dependent on JAK2-Stat5 and p38MAPK signaling. Our study identifies potential targets for treating CCL2-dependent metastasis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CCL2, MICE, MIGRATION, LUNG, CANCER-CELLS, MYELOID CELLS, TUMOR-METASTASIS, INFLAMMATORY MONOCYTES, CHEMOKINE RECEPTOR 2, L-SELECTIN
journal title
CANCER CELL
Cancer Cell
volume
22
issue
1
pages
91 - 105
Web of Science type
Article
Web of Science id
000306395300011
JCR category
ONCOLOGY
JCR impact factor
24.755 (2012)
JCR rank
4/196 (2012)
JCR quartile
1 (2012)
ISSN
1535-6108
DOI
10.1016/j.ccr.2012.05.023
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2976334
handle
http://hdl.handle.net/1854/LU-2976334
date created
2012-08-29 12:55:06
date last changed
2012-09-04 11:13:10
@article{2976334,
  abstract     = {Increased expression of the chemokine CCL2 in tumor cells correlates with enhanced metastasis, poor prognosis, and recruitment of CCR2(+)Ly6C(hi) monocytes. However, the mechanisms driving tumor cell extravasation through the endothelium remain elusive. Here, we describe CCL2 upregulation in metastatic UICC stage IV colon carcinomas and demonstrate that tumor cell-derived CCL2 activates the CCR2(+) endothelium to increase vascular permeability in vivo. CCR2 deficiency prevents colon carcinoma extravasation and metastasis. Of note, CCR2 expression on radio-resistant cells or endothelial CCR2 expression restores extravasation and metastasis in Ccr2(-/-) mice. Reduction of CCR2 expression on myeloid cells decreases but does not prevent metastasis. CCL2-induced vascular permeability and metastasis is dependent on JAK2-Stat5 and p38MAPK signaling. Our study identifies potential targets for treating CCL2-dependent metastasis.},
  author       = {Wolf, Monika Julia and Hoos, Alexandra and Bauer, Judith and Boettcher, Steffen and Knust, Markus and Weber, Achim and Simonavicius, Nicole and Schneider, Christoph and Lang, Matthias and Sturzl, Michael and Croner, Roland S and Konrad, Andreas and Manz, Markus G and Moch, Holger and Aguzzi, Adriano and van Loo, Geert and Pasparakis, Manolis and Prinz, Marco and Borsig, Lubor and Heikenwalder, Mathias},
  issn         = {1535-6108},
  journal      = {CANCER CELL},
  keyword      = {CCL2,MICE,MIGRATION,LUNG,CANCER-CELLS,MYELOID CELLS,TUMOR-METASTASIS,INFLAMMATORY MONOCYTES,CHEMOKINE RECEPTOR 2,L-SELECTIN},
  language     = {eng},
  number       = {1},
  pages        = {91--105},
  title        = {Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway},
  url          = {http://dx.doi.org/10.1016/j.ccr.2012.05.023},
  volume       = {22},
  year         = {2012},
}

Chicago
Wolf, Monika Julia, Alexandra Hoos, Judith Bauer, Steffen Boettcher, Markus Knust, Achim Weber, Nicole Simonavicius, et al. 2012. “Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway.” Cancer Cell 22 (1): 91–105.
APA
Wolf, M. J., Hoos, A., Bauer, J., Boettcher, S., Knust, M., Weber, A., Simonavicius, N., et al. (2012). Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. CANCER CELL, 22(1), 91–105.
Vancouver
1.
Wolf MJ, Hoos A, Bauer J, Boettcher S, Knust M, Weber A, et al. Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. CANCER CELL. 2012;22(1):91–105.
MLA
Wolf, Monika Julia, Alexandra Hoos, Judith Bauer, et al. “Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway.” CANCER CELL 22.1 (2012): 91–105. Print.