Document Detail


Natriuretic peptide receptor A signaling regulates stem cell recruitment and angiogenesis: a model to study linkage between inflammation and tumorigenesis.
MedLine Citation:
PMID:  23533187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Natriuretic peptide receptor A (NPRA), the signaling receptor for the cardiac hormone, atrial natriuretic peptide (ANP), is expressed abundantly in inflamed/injured tissues and tumors. NPRA deficiency substantially decreases tissue inflammation and inhibits tumor growth. However, the precise mechanism of NPRA function and whether it links inflammation and tumorigenesis remains unknown. Since both injury repair and tumor growth require stem cell recruitment and angiogenesis, we examined the role of NPRA signaling in tumor angiogenesis as a model of tissue injury repair in this study. In in vitro cultures, aortas from NPRA-KO mice show significantly lower angiogenic response compared to wild-type counterparts. The NPRA antagonist that decreases NPRA expression, inhibits lipopolysaccharide-induced angiogenesis. The reduction in angiogenesis correlates with decreased expression of vascular endothelial growth factor and chemokine (C-X-C motif) receptor 4 (CXCR4) implicating a cell recruitment defect. To test whether NPRA regulates migration of cells to tumors, mesenchymal stem cells (MSCs) were administered i.v., and the results showed that MSCs fail to migrate to the tumor microenvironment in NPRA-KO mice. However, coimplanting tumor cells with MSCs increases angiogenesis and tumorigenesis in NPRA-KO mice, in part by promoting expression of CXCR4 and its ligand, stromal cell-derived factor 1α. Taken together, these results demonstrate that NPRA signaling regulates stem cell recruitment and angiogenesis leading to tumor growth. Thus, NPRA signaling provides a key linkage between inflammation and tumorigenesis, and NPRA may be a target for drug development against cancers and tissue injury repair.
Authors:
Jaya Mallela; Sowndharya Ravi; Frantz Jean Louis; Bianca Mulaney; Michael Cheung; Ujjwala Sree Garapati; Vignesh Chinnasamy; Chunyan Wang; Srinivas Nagaraj; Shyam S Mohapatra; Subhra Mohapatra
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  31     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-08     Completed Date:  2014-05-12     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1321-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 AlphaMed Press.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinogenesis / genetics,  metabolism*,  pathology
Carcinoma, Lewis Lung / blood supply*,  genetics,  metabolism*,  pathology
Female
Immunohistochemistry
Inflammation / metabolism,  pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Pathologic / metabolism,  pathology
Receptors, Atrial Natriuretic Factor / genetics,  metabolism*
Signal Transduction
Stem Cells / cytology*,  metabolism*
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
5R01CA152005/CA/NCI NIH HHS; R01 CA152005/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 4.6.1.2/Receptors, Atrial Natriuretic Factor; EC 4.6.1.2/atrial natriuretic factor receptor A
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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