Natriuretic Peptide Receptor A Signaling Regulates Stem Cell Recruitment and Angiogenesis: A Model to Study Linkage Between Inflammation and Tumorigenesis

• DOI: 10.1002/stem.1376
• Publication Date: 2013-03-26T13:56:30Z
• Authors: Jaya Mallela; Sowndharya Ravi; Frantz Jean Louis; Bianca Mulaney; Michael Cheung; Ujjwala Sree Gara...; Vignesh Chinnasamy; Chunyan Wang; Srinivas Nagaraj; Shyam S. Mohapatra; Subhra Mohapatra
• Keywords: Inflammation; Mice, Knockout; 0301 basic medicine; Neovascularization, Pathologic; Carcinogenesis; Stem Cells; Immunohistochemistry; 3. Good health; Mice, Inbred C57BL; Carcinoma, Lewis Lung; Mice; 03 medical and health sciences; Tumor Microenvironment; Animals; Female; Receptors, Atrial Natriuretic Factor; Signal Transduction

Abstract Natriuretic peptide receptor A (NPRA), the signaling for cardiac hormone, atrial natriuretic (ANP), is expressed abundantly in inflamed/injured tissues and tumors. NPRA deficiency substantially decreases tissue inflammation inhibits tumor growth. However, precise mechanism of function whether it links tumorigenesis remains unknown. Since both injury repair growth require stem cell recruitment angiogenesis, we examined role angiogenesis as a model this study. In vitro cultures, aortas from NPRA-KO mice show significantly lower angiogenic response compared to wild-type counterparts. The antagonist that expression, lipopolysaccharide-induced angiogenesis. reduction correlates with decreased expression vascular endothelial factor chemokine (C-X-C motif) 4 (CXCR4) implicating defect. To test regulates migration cells tumors, mesenchymal (MSCs) were administered i.v., results showed MSCs fail migrate microenvironment mice. coimplanting increases mice, part by promoting CXCR4 its ligand, stromal cell-derived 1α. Taken together, these demonstrate leading Thus, provides key linkage between tumorigenesis, may be target drug development against cancers repair.