Differential expression of stem cell markers and vascular endothelial growth factor in human retinoblastoma tissue.
OBJECTIVE
To investigate the relationship between vascular endothelial growth factor (VEGF) and the cancer stem cell-vascular niche complex in human retinoblastoma tissue.


METHODS
Six human retinoblastoma specimens primarily enucleated for Reese-Ellsworth classification stage 5a were stained to detect cancer stem cell markers, including ABCG2 for the stem cell marker and MCM2 for the neural stem cell marker, as well as to detect VEGF for the angiogenic cytokine. Using immunofluorescence, the expression of these proteins was analyzed, and their relative locations noted.


RESULTS
In non-neoplastic retina of tumor-bearing eyes, ABCG2 and MCM2 were sporadically expressed in the ganglion cell layer and the inner nuclear layer, whereas VEGF was sporadically expressed in inner retina where retinal vessels are abundantly distributed. In the tumor, ABCG2 was strongly expressed out of Wintersteiner rosettes, whereas MCM2 and VEGF were strongly stained in the rosettes. Interestingly, the outer portion of the rosettes was positive for MCM2, and the inner portion of the rosettes was positive for VEGF.


CONCLUSIONS
Our data demonstrated that MCM2 and VEGF are strongly expressed in the rosettes of the tumor, which were far from the area of ABCG2-positive cells. Although VEGF might not directly contribute to the cancer stem cell-vascular niche complex, it could play some role in the differentiation of tumor cells to build up the rosettes.
Kim
Martha
M
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
Kim
Jeong Hun
JH
Kim
Jin Hyoung
JH
Kim
Dong Hun
DH
Yu
Young Suk
YS
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D012160:Retina / Q000378:metabolism; D019572:Retinal Neoplasms / Q000378:metabolism*; D012175:Retinoblastoma / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D042461:Vascular Endothelial Growth Factor A; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2