Document Detail


Dysfunctional endothelial cells directly stimulate cancer inflammation and metastasis.
MedLine Citation:
PMID:  23463345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the influence of context-dependent endothelial cell (EC) regulation of vascular disease and repair is well-established, the privileged roles ECs play as paracrine regulators of tumor progression has only recently become appreciated. We hypothesized that if the same endothelial physiology governs vascular and cancer biology then EC control in cancer should follow endothelial regulation of vascular health. Healthy ECs promote vascular repair and inhibit tumor invasiveness and metastasis. Dysfunctional ECs have the opposite effects in vascular disease, and we now ask if dysfunctionally activated ECs will promote cancer cell inflammatory signaling and aggressive properties. Indeed, while factors released from quiescent ECs induce balanced inflammatory signaling, correlating with decreased proliferation and invasiveness, factors released from dysfunctional ECs robustly activated NF-κB and STAT3 signaling within cancer cells, correlating with increased in vitro invasiveness and decreased proliferation and survival. Furthermore, matrix-embedded dysfunctional ECs stimulated intratumoral pro-inflammatory signaling and spontaneous metastasis, while simultaneously slowing primary tumor growth, when implanted adjacent to Lewis lung carcinoma tumors. These studies may broaden our appreciation of the roles of endothelial function and dysfunction, increase understanding and control of the tumor microenvironment, and facilitate optimization of anti-angiogenic and vascular-modifying therapies in cancer and other diseases.
Authors:
Joseph W Franses; Natalia C Drosu; William J Gibson; Vipul C Chitalia; Elazer R Edelman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-08
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-07-09     Completed Date:  2013-09-12     Revised Date:  2014-10-01    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1334-44     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Cell Proliferation
Cells, Cultured
Endothelial Cells / physiology*
Female
Humans
Inflammation / etiology*
Mice
Mice, Inbred C57BL
Neoplasm Invasiveness
Neoplasm Metastasis*
Neoplasms / pathology*
Phenotype
Transcriptome
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
1K08DK080946/DK/NIDDK NIH HHS; K08 DK080946/DK/NIDDK NIH HHS; R01 GM49039/GM/NIGMS NIH HHS; R01 HL060407/HL/NHLBI NIH HHS; T32 GM007753/GM/NIGMS NIH HHS; T32GM007753/GM/NIGMS NIH HHS
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