CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F19%3A00071048" target="_blank" >RIV/00159816:_____/19:00071048 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/19:00107961
Result on the web
<a href="https://mcr.aacrjournals.org/content/17/3/783" target="_blank" >https://mcr.aacrjournals.org/content/17/3/783</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/1541-7786.MCR-18-0530" target="_blank" >10.1158/1541-7786.MCR-18-0530</a>
Alternative languages
Result language
angličtina
Original language name
CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis
Original language description
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 endothelialspecific Ccr2-deficient mouse model (Ccr2(ec)KO). Similar levels of circulating monocytes and equal leukocyte recruitment to metastatic lesions of Ccr2(ec)KO and Ccr2(fl/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 Ccr2(ec)KO and Ccr2(fl/f)l littermates the absence of vascular permeability induction was observed only in Ccr2(ec)KO 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. Implications: 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/GJ17-08985Y" target="_blank" >GJ17-08985Y: c-Myb-regulated inflammatory circuit in basal-like mammary tumors</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
MOLECULAR CANCER RESEARCH
ISSN
1541-7786
e-ISSN
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Volume of the periodical
17
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
783-793
UT code for WoS article
000460099800012
EID of the result in the Scopus database
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