---
_id: '6190'
abstract:
- lang: eng
  text: "Increased levels of the chemokine CCL2 in cancer patients are associated
    with poor prognosis. Experimental evidence suggests that CCL2 correlates with
    inflammatory monocyte recruitment and induction of vascular activation, but the
    functionality remains open. Here, we show that endothelial Ccr2 facilitates pulmonary
    metastasis using an endothelial-specific Ccr2-deficient mouse model (Ccr2ecKO).
    Similar levels of circulating monocytes and equal leukocyte recruitment to metastatic
    lesions of Ccr2ecKO and Ccr2fl/fl littermates were observed. The absence of endothelial
    Ccr2 strongly reduced pulmonary metastasis, while the primary tumor growth was
    unaffected. Despite a comparable cytokine milieu in Ccr2ecKO and Ccr2fl/fl littermates
    the absence of vascular permeability induction was observed only in Ccr2ecKO mice.
    CCL2 stimulation of pulmonary endothelial cells resulted in increased phosphorylation
    of MLC2, endothelial cell retraction, and vascular leakiness that was blocked
    by an addition of a CCR2 inhibitor. These data demonstrate that endothelial CCR2
    expression is required for tumor cell extravasation and pulmonary metastasis.\r\n\r\nImplications:
    The findings provide mechanistic insight into how CCL2–CCR2 signaling in endothelial
    cells promotes their activation through myosin light chain phosphorylation, resulting
    in endothelial retraction and enhanced tumor cell migration and metastasis."
article_processing_charge: No
article_type: original
author:
- first_name: Marko
  full_name: Roblek, Marko
  id: 3047D808-F248-11E8-B48F-1D18A9856A87
  last_name: Roblek
  orcid: 0000-0001-9588-1389
- first_name: Darya
  full_name: Protsyuk, Darya
  last_name: Protsyuk
- first_name: Paul F.
  full_name: Becker, Paul F.
  last_name: Becker
- first_name: Cristina
  full_name: Stefanescu, Cristina
  last_name: Stefanescu
- first_name: Christian
  full_name: Gorzelanny, Christian
  last_name: Gorzelanny
- first_name: Jesus F.
  full_name: Glaus Garzon, Jesus F.
  last_name: Glaus Garzon
- first_name: Lucia
  full_name: Knopfova, Lucia
  last_name: Knopfova
- first_name: Mathias
  full_name: Heikenwalder, Mathias
  last_name: Heikenwalder
- first_name: Bruno
  full_name: Luckow, Bruno
  last_name: Luckow
- first_name: Stefan W.
  full_name: Schneider, Stefan W.
  last_name: Schneider
- first_name: Lubor
  full_name: Borsig, Lubor
  last_name: Borsig
citation:
  ama: Roblek M, Protsyuk D, Becker PF, et al. CCL2 is a vascular permeability factor
    inducing CCR2-dependent endothelial retraction during lung metastasis. <i>Molecular
    Cancer Research</i>. 2019;17(3):783-793. doi:<a href="https://doi.org/10.1158/1541-7786.MCR-18-0530">10.1158/1541-7786.MCR-18-0530</a>
  apa: Roblek, M., Protsyuk, D., Becker, P. F., Stefanescu, C., Gorzelanny, C., Glaus
    Garzon, J. F., … Borsig, L. (2019). CCL2 is a vascular permeability factor inducing
    CCR2-dependent endothelial retraction during lung metastasis. <i>Molecular Cancer
    Research</i>. AACR. <a href="https://doi.org/10.1158/1541-7786.MCR-18-0530">https://doi.org/10.1158/1541-7786.MCR-18-0530</a>
  chicago: Roblek, Marko, Darya Protsyuk, Paul F. Becker, Cristina Stefanescu, Christian
    Gorzelanny, Jesus F. Glaus Garzon, Lucia Knopfova, et al. “CCL2 Is a Vascular
    Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung
    Metastasis.” <i>Molecular Cancer Research</i>. AACR, 2019. <a href="https://doi.org/10.1158/1541-7786.MCR-18-0530">https://doi.org/10.1158/1541-7786.MCR-18-0530</a>.
  ieee: M. Roblek <i>et al.</i>, “CCL2 is a vascular permeability factor inducing
    CCR2-dependent endothelial retraction during lung metastasis,” <i>Molecular Cancer
    Research</i>, vol. 17, no. 3. AACR, pp. 783–793, 2019.
  ista: Roblek M, Protsyuk D, Becker PF, Stefanescu C, Gorzelanny C, Glaus Garzon
    JF, Knopfova L, Heikenwalder M, Luckow B, Schneider SW, Borsig L. 2019. CCL2 is
    a vascular permeability factor inducing CCR2-dependent endothelial retraction
    during lung metastasis. Molecular Cancer Research. 17(3), 783–793.
  mla: Roblek, Marko, et al. “CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent
    Endothelial Retraction during Lung Metastasis.” <i>Molecular Cancer Research</i>,
    vol. 17, no. 3, AACR, 2019, pp. 783–93, doi:<a href="https://doi.org/10.1158/1541-7786.MCR-18-0530">10.1158/1541-7786.MCR-18-0530</a>.
  short: M. Roblek, D. Protsyuk, P.F. Becker, C. Stefanescu, C. Gorzelanny, J.F. Glaus
    Garzon, L. Knopfova, M. Heikenwalder, B. Luckow, S.W. Schneider, L. Borsig, Molecular
    Cancer Research 17 (2019) 783–793.
date_created: 2019-03-31T21:59:12Z
date_published: 2019-03-01T00:00:00Z
date_updated: 2023-08-25T08:57:01Z
day: '01'
department:
- _id: DaSi
doi: 10.1158/1541-7786.MCR-18-0530
external_id:
  isi:
  - '000460099800012'
  pmid:
  - '30552233'
intvolume: '        17'
isi: 1
issue: '3'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1158/1541-7786.MCR-18-0530
month: '03'
oa: 1
oa_version: Published Version
page: 783-793
pmid: 1
publication: Molecular Cancer Research
publication_identifier:
  eissn:
  - '15573125'
  issn:
  - '15417786'
publication_status: published
publisher: AACR
quality_controlled: '1'
scopus_import: '1'
status: public
title: CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial
  retraction during lung metastasis
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
year: '2019'
...