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Title: Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation

Abstract

Growing evidence indicates that inducible cyclooxygenase-2 (COX-2) is involved in the pathogenesis of inflammatory disorders and various types of cancer. Endothelial progenitor cells recruited from the bone marrow have been shown to be involved in the formation of new vessels in malignancies and discussed for being a key point in tumour progression and metastasis. However, until now, nothing is known about an interaction between COX and endothelial progenitor cells (EPC). Expression of COX-1 and COX-2 was detected by semiquantitative RT-PCR and Western blot. Proliferation kinetics, cell cycle distribution and rate of apoptosis were analysed by MTT test and FACS analysis. Further analyses revealed an implication of Akt phosphorylation and caspase-3 activation. Both COX-1 and COX-2 expression can be found in bone-marrow-derived endothelial progenitor cells in vitro. COX-2 inhibition leads to a significant reduction in proliferation of endothelial progenitor cells by an increase in apoptosis and cell cycle arrest. COX-2 inhibition leads further to an increased cleavage of caspase-3 protein and inversely to inhibition of Akt activation. Highly proliferating endothelial progenitor cells can be targeted by selective COX-2 inhibition in vitro. These results indicate that upcoming therapy strategies in cancer patients targeting COX-2 may be effective in inhibiting tumour vasculogenesis asmore » well as angiogenic processes.« less

Authors:
 [1];  [2];  [2];  [3]
  1. Pneumology Service-Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck (Austria)
  2. Inflammation Research, Laboratory Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck (Austria)
  3. Pneumology Service-Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck (Austria). E-mail: C.M.Kaehler@uibk.ac.at
Publication Date:
OSTI Identifier:
20858020
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 312; Journal Issue: 15; Other Information: DOI: 10.1016/j.yexcr.2006.05.021; PII: S0014-4827(06)00204-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BONE MARROW; CELL CYCLE; CELL PROLIFERATION; IN VITRO; INFLAMMATION; INHIBITION; METASTASES; NEOPLASMS; PATHOGENESIS; PATIENTS; PHOSPHORYLATION; POLYMERASE CHAIN REACTION; PROTEINS

Citation Formats

Colleselli, Daniela, Bijuklic, Klaudija, Mosheimer, Birgit A., and Kaehler, Christian M.. Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation. United States: N. p., 2006. Web. doi:10.1016/j.yexcr.2006.05.021.
Colleselli, Daniela, Bijuklic, Klaudija, Mosheimer, Birgit A., & Kaehler, Christian M.. Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation. United States. doi:10.1016/j.yexcr.2006.05.021.
Colleselli, Daniela, Bijuklic, Klaudija, Mosheimer, Birgit A., and Kaehler, Christian M.. Sun . "Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation". United States. doi:10.1016/j.yexcr.2006.05.021.
@article{osti_20858020,
title = {Inhibition of cyclooxygenase (COX)-2 affects endothelial progenitor cell proliferation},
author = {Colleselli, Daniela and Bijuklic, Klaudija and Mosheimer, Birgit A. and Kaehler, Christian M.},
abstractNote = {Growing evidence indicates that inducible cyclooxygenase-2 (COX-2) is involved in the pathogenesis of inflammatory disorders and various types of cancer. Endothelial progenitor cells recruited from the bone marrow have been shown to be involved in the formation of new vessels in malignancies and discussed for being a key point in tumour progression and metastasis. However, until now, nothing is known about an interaction between COX and endothelial progenitor cells (EPC). Expression of COX-1 and COX-2 was detected by semiquantitative RT-PCR and Western blot. Proliferation kinetics, cell cycle distribution and rate of apoptosis were analysed by MTT test and FACS analysis. Further analyses revealed an implication of Akt phosphorylation and caspase-3 activation. Both COX-1 and COX-2 expression can be found in bone-marrow-derived endothelial progenitor cells in vitro. COX-2 inhibition leads to a significant reduction in proliferation of endothelial progenitor cells by an increase in apoptosis and cell cycle arrest. COX-2 inhibition leads further to an increased cleavage of caspase-3 protein and inversely to inhibition of Akt activation. Highly proliferating endothelial progenitor cells can be targeted by selective COX-2 inhibition in vitro. These results indicate that upcoming therapy strategies in cancer patients targeting COX-2 may be effective in inhibiting tumour vasculogenesis as well as angiogenic processes.},
doi = {10.1016/j.yexcr.2006.05.021},
journal = {Experimental Cell Research},
number = 15,
volume = 312,
place = {United States},
year = {Sun Sep 10 00:00:00 EDT 2006},
month = {Sun Sep 10 00:00:00 EDT 2006}
}