Cargando…
Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells
BACKGROUND: Infantile hemangiomas are benign vascular tumors primarily found on the skin in 10% of the pediatric population. The etiology of this disease is largely unknown and while large scale genomic studies have examined the transcriptomes of infantile hemangioma tumors as a whole, no study to d...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655845/ https://www.ncbi.nlm.nih.gov/pubmed/23531100 http://dx.doi.org/10.1186/2045-824X-5-6 |
_version_ | 1782269933309132800 |
---|---|
author | Stiles, Jessica M Rowntree, Rebecca K Amaya, Clarissa Diaz, Dolores Kokta, Victor Mitchell, Dianne C Bryan, Brad A |
author_facet | Stiles, Jessica M Rowntree, Rebecca K Amaya, Clarissa Diaz, Dolores Kokta, Victor Mitchell, Dianne C Bryan, Brad A |
author_sort | Stiles, Jessica M |
collection | PubMed |
description | BACKGROUND: Infantile hemangiomas are benign vascular tumors primarily found on the skin in 10% of the pediatric population. The etiology of this disease is largely unknown and while large scale genomic studies have examined the transcriptomes of infantile hemangioma tumors as a whole, no study to date has compared the global gene expression profiles of pure infantile hemangioma endothelial cells (HEMECs) to that of normal human dermal microvascular endothelial cells (HDMVECs). METHODS: To shed light on the molecular differences between these normal and aberrant dermal endothelial cell types, we performed whole genome microarray analysis on purified cultures of HEMECs and HDMVECs. We then utilized qPCR and immunohistochemistry to confirm our microarray results. RESULTS: Our array analysis identified 125 genes whose expression was upregulated and 104 genes whose expression was downregulated by greater than two fold in HEMECs compared to HDMVECs. Bioinformatics analysis revealed three major classifications of gene functions that were altered in HEMECs including cell adhesion, cell cycle, and arachidonic acid production. Several of these genes have been reported to be critical regulators and/or mutated in cancer, vascular tumors, and vascular malformations. We confirmed the expression of a subset of these differentially expressed genes (ANGPT2, ANTXR1, SMARCE1, RGS5, CTAG2, LTBP2, CLDN11, and KISS1) using qPCR and utilized immunohistochemistry on a panel of paraffin embedded infantile hemangioma tumor tissues to demonstrate that the cancer/testis antigen CTAG2 is highly abundant in vessel-dense proliferating infantile hemangiomas and with significantly reduced levels during tumor involution as vascular density decreases. CONCLUSION: Our data reveal that the transcriptome of HEMECs is reflective of a pro-proliferative cell type with altered adhesive characteristics. Moveover, HEMECs show altered expression of many genes that are important in the progression and prognosis of metastatic cancers. |
format | Online Article Text |
id | pubmed-3655845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36558452013-05-17 Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells Stiles, Jessica M Rowntree, Rebecca K Amaya, Clarissa Diaz, Dolores Kokta, Victor Mitchell, Dianne C Bryan, Brad A Vasc Cell Research BACKGROUND: Infantile hemangiomas are benign vascular tumors primarily found on the skin in 10% of the pediatric population. The etiology of this disease is largely unknown and while large scale genomic studies have examined the transcriptomes of infantile hemangioma tumors as a whole, no study to date has compared the global gene expression profiles of pure infantile hemangioma endothelial cells (HEMECs) to that of normal human dermal microvascular endothelial cells (HDMVECs). METHODS: To shed light on the molecular differences between these normal and aberrant dermal endothelial cell types, we performed whole genome microarray analysis on purified cultures of HEMECs and HDMVECs. We then utilized qPCR and immunohistochemistry to confirm our microarray results. RESULTS: Our array analysis identified 125 genes whose expression was upregulated and 104 genes whose expression was downregulated by greater than two fold in HEMECs compared to HDMVECs. Bioinformatics analysis revealed three major classifications of gene functions that were altered in HEMECs including cell adhesion, cell cycle, and arachidonic acid production. Several of these genes have been reported to be critical regulators and/or mutated in cancer, vascular tumors, and vascular malformations. We confirmed the expression of a subset of these differentially expressed genes (ANGPT2, ANTXR1, SMARCE1, RGS5, CTAG2, LTBP2, CLDN11, and KISS1) using qPCR and utilized immunohistochemistry on a panel of paraffin embedded infantile hemangioma tumor tissues to demonstrate that the cancer/testis antigen CTAG2 is highly abundant in vessel-dense proliferating infantile hemangiomas and with significantly reduced levels during tumor involution as vascular density decreases. CONCLUSION: Our data reveal that the transcriptome of HEMECs is reflective of a pro-proliferative cell type with altered adhesive characteristics. Moveover, HEMECs show altered expression of many genes that are important in the progression and prognosis of metastatic cancers. BioMed Central 2013-03-25 /pmc/articles/PMC3655845/ /pubmed/23531100 http://dx.doi.org/10.1186/2045-824X-5-6 Text en Copyright © 2013 Stiles et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Stiles, Jessica M Rowntree, Rebecca K Amaya, Clarissa Diaz, Dolores Kokta, Victor Mitchell, Dianne C Bryan, Brad A Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
title | Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
title_full | Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
title_fullStr | Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
title_full_unstemmed | Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
title_short | Gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
title_sort | gene expression analysis reveals marked differences in the transcriptome of infantile hemangioma endothelial cells compared to normal dermal microvascular endothelial cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655845/ https://www.ncbi.nlm.nih.gov/pubmed/23531100 http://dx.doi.org/10.1186/2045-824X-5-6 |
work_keys_str_mv | AT stilesjessicam geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells AT rowntreerebeccak geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells AT amayaclarissa geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells AT diazdolores geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells AT koktavictor geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells AT mitchelldiannec geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells AT bryanbrada geneexpressionanalysisrevealsmarkeddifferencesinthetranscriptomeofinfantilehemangiomaendothelialcellscomparedtonormaldermalmicrovascularendothelialcells |