Abstract |
Lymphangiogenesis is implicated in lymphatic metastasis of tumor cells. Recently, growing evidences show that endothelial progenitor cells (EPCs) are involved in lymphangiogenesis. This study has investigated effects of VEGF-C/VEGFR-3 ( vascular endothelial growth factor receptor-3) signaling pathway on EPC differentiation and effectiveness of inhibiting lymphatic formation of EPCs with VEGFR-3 siRNA delivered in PEI ( polyethylenimine)- alginate nanoparticles. CD34(+)VEGFR-3(+) EPCs were sorted from mononuclear cells of human cord blood. Under induction with VEGF-C, the cells differentiated toward lymphatic endothelial cells. The nanoparticles were formulated with 25 kDa branched PEI and alginate. The size and surface charge of PEI- alginate nanoparticles loading VEGFR-3 siRNA (N/P = 16) are 139.1 nm and 7.56 mV respectively. VEGFR-3 siRNA specifically inhibited expression of VEGFR-3 mRNA in the cells. After treatment with PEI- alginate/ siRNA nanocomplexes, EPCs could not differentiate into lymphatic endothelial cells, and proliferation, migration and lymphatic formation of EPC-derived cells were suppressed significantly. These results demonstrate that VEGFR-3 signaling plays an important role in differentiation of CD34(+)VEGFR-3(+) EPCs. VEGFR-3 siRNA delivered with PEI- alginate nanoparticles can effectively inhibit differentiation and lymphangiogenesis of EPCs. Inhibiting VEGFR-3 signaling with siRNA/nanocomplexes would be a potential therapy for suppression of tumor lymphangiogenesis and lymphatic metastasis.
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Authors | Ting Li, Guo-dong Wang, Yu-zhen Tan, Hai-jie Wang |
Journal | International journal of biological sciences
(Int J Biol Sci)
Vol. 10
Issue 2
Pg. 160-70
( 2014)
ISSN: 1449-2288 [Electronic] Australia |
PMID | 24520214
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Alginates
- Antigens, CD34
- Hexuronic Acids
- RNA, Small Interfering
- Glucuronic Acid
- Polyethyleneimine
- Vascular Endothelial Growth Factor Receptor-3
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Topics |
- Alginates
- Antigens, CD34
(metabolism)
- Cell Differentiation
(genetics)
- Cell Movement
- Endothelial Cells
(cytology, ultrastructure)
- Fetal Blood
(cytology)
- Glucuronic Acid
- Hexuronic Acids
- Humans
- Lymphangiogenesis
(genetics)
- Microscopy, Electron, Scanning
- Nanoparticles
- Polyethyleneimine
- RNA Interference
- RNA, Small Interfering
- Stem Cells
(cytology, ultrastructure)
- Vascular Endothelial Growth Factor Receptor-3
(antagonists & inhibitors, genetics, metabolism)
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