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Title: Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis

Abstract

Although investigations of mature normal and tumor-derived capillaries have resulted in characterization of these structures at the phenotypic level, less is known regarding the initial molecular cues for cellular assembly of endothelial cells into human capillaries. Here, we employ a novel combination of microenvironmental manipulation and microarray data filtration over narrowly delineated temporal data series to identify the morphogenesis component apart from the proliferation component, as pooled human microvascular-derived endothelial cells are induced to form capillary-like structures in vitro in a murine tumor-derived matrix. The 217 morphogenesis-specific genes identified using this subtractive transcriptomics approach are mostly independent of the angiogenic proteins currently used as therapeutic targets for aberrant angiogenesis. Quantitative real-time PCR was used to validate 20% of these transcripts. Immunofluorescent analysis of proliferating and tube-forming cells validates at the protein level the morphogenesis-specific expression pattern of 16 of the 217 gene products identified. The transcripts that are selectively up-regulated in tube-forming endothelial cells reveal a temporal expression pattern of genes primarily associated with intracellular trafficking, guided migration, cytoskeletal reorganization, cellular adhesion, and proliferation inhibition. These data show that a sequential upregulation of genes that establish and maintain polarity occurs during migration and morphogenesis of in vitro human endothelial cellsmore » undergoing tubulogenesis; some of which may well be effective as novel antiangiogenic drug targets.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
917221
Report Number(s):
ANL/BIO/JA-54409
Journal ID: ISSN 0008-5472; CNREA8; TRN: US200816%%438
DOE Contract Number:  
DE-AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cancer Res.; Journal Volume: 66; Journal Issue: 8 ; Apr. 15, 2006
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION; ADHESION; CAPILLARIES; FILTRATION; GENES; IN VITRO; MORPHOGENESIS; PROLIFERATION; PROTEINS; TARGETS

Citation Formats

Glesne, D. A., Zhang, W., Mandava, S., Ursos, L., Buell, M. E., Makowski, L., Rodi, D. J., and Biosciences Division. Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis. United States: N. p., 2006. Web. doi:10.1158/0008-5472.CAN-05-3294.
Glesne, D. A., Zhang, W., Mandava, S., Ursos, L., Buell, M. E., Makowski, L., Rodi, D. J., & Biosciences Division. Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis. United States. doi:10.1158/0008-5472.CAN-05-3294.
Glesne, D. A., Zhang, W., Mandava, S., Ursos, L., Buell, M. E., Makowski, L., Rodi, D. J., and Biosciences Division. Sat . "Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis". United States. doi:10.1158/0008-5472.CAN-05-3294.
@article{osti_917221,
title = {Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis},
author = {Glesne, D. A. and Zhang, W. and Mandava, S. and Ursos, L. and Buell, M. E. and Makowski, L. and Rodi, D. J. and Biosciences Division},
abstractNote = {Although investigations of mature normal and tumor-derived capillaries have resulted in characterization of these structures at the phenotypic level, less is known regarding the initial molecular cues for cellular assembly of endothelial cells into human capillaries. Here, we employ a novel combination of microenvironmental manipulation and microarray data filtration over narrowly delineated temporal data series to identify the morphogenesis component apart from the proliferation component, as pooled human microvascular-derived endothelial cells are induced to form capillary-like structures in vitro in a murine tumor-derived matrix. The 217 morphogenesis-specific genes identified using this subtractive transcriptomics approach are mostly independent of the angiogenic proteins currently used as therapeutic targets for aberrant angiogenesis. Quantitative real-time PCR was used to validate 20% of these transcripts. Immunofluorescent analysis of proliferating and tube-forming cells validates at the protein level the morphogenesis-specific expression pattern of 16 of the 217 gene products identified. The transcripts that are selectively up-regulated in tube-forming endothelial cells reveal a temporal expression pattern of genes primarily associated with intracellular trafficking, guided migration, cytoskeletal reorganization, cellular adhesion, and proliferation inhibition. These data show that a sequential upregulation of genes that establish and maintain polarity occurs during migration and morphogenesis of in vitro human endothelial cells undergoing tubulogenesis; some of which may well be effective as novel antiangiogenic drug targets.},
doi = {10.1158/0008-5472.CAN-05-3294},
journal = {Cancer Res.},
number = 8 ; Apr. 15, 2006,
volume = 66,
place = {United States},
year = {Sat Apr 15 00:00:00 EDT 2006},
month = {Sat Apr 15 00:00:00 EDT 2006}
}