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Identification of tumor endothelial cells with high aldehyde dehydrogenase activity and a highly angiogenic phenotype.
- Source :
-
PloS one [PLoS One] 2014 Dec 01; Vol. 9 (12), pp. e113910. Date of Electronic Publication: 2014 Dec 01 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Tumor blood vessels play an important role in tumor progression and metastasis. It has been reported that tumor endothelial cells (TECs) exhibit highly angiogenic phenotypes compared with those of normal endothelial cells (NECs). TECs show higher proliferative and migratory abilities than those NECs, together with upregulation of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2). Furthermore, compared with NECs, stem cell markers such as Sca-1, CD90, and multidrug resistance 1 are upregulated in TECs, suggesting that stem-like cells exist in tumor blood vessels. In this study, to reveal the biological role of stem-like TECs, we analyzed expression of the stem cell marker aldehyde dehydrogenase (ALDH) in TECs and characterized ALDHhigh TECs. TECs and NECs were isolated from melanoma-xenografted nude mice and normal dermis, respectively. ALDH mRNA expression and activity were higher in TECs than those in NECs. Next, ALDHhigh/low TECs were isolated by fluorescence-activated cell sorting to compare their characteristics. Compared with ALDHlow TECs, ALDHhigh TECs formed more tubes on Matrigel-coated plates and sustained the tubular networks longer. Furthermore, VEGFR2 expression was higher in ALDHhigh TECs than that in ALDHlow TECs. In addition, ALDH was expressed in the tumor blood vessels of in vivo mouse models of melanoma and oral carcinoma, but not in normal blood vessels. These findings indicate that ALDHhigh TECs exhibit an angiogenic phenotype. Stem-like TECs may have an essential role in tumor angiogenesis.
- Subjects :
- Aldehyde Dehydrogenase analysis
Aldehyde Dehydrogenase genetics
Animals
Cell Line
Endothelial Cells enzymology
Endothelial Cells metabolism
Gene Expression Regulation, Neoplastic
Humans
Melanoma genetics
Mice, Nude
Neovascularization, Pathologic genetics
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A analysis
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor Receptor-2 analysis
Vascular Endothelial Growth Factor Receptor-2 genetics
Aldehyde Dehydrogenase metabolism
Endothelial Cells pathology
Melanoma enzymology
Melanoma pathology
Neovascularization, Pathologic enzymology
Neovascularization, Pathologic pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25437864
- Full Text :
- https://doi.org/10.1371/journal.pone.0113910