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

Journal Article · Sun Sep 10 00:00:00 EDT 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.05.021· OSTI ID:20858020

Colleselli, Daniela ^[1]; Bijuklic, Klaudija ^[2]; Mosheimer, Birgit A ^[2]; Kaehler, Christian M ^[1]

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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)

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.

• OSTI ID: 20858020
• Journal Information: Experimental Cell Research, Vol. 312, 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); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BONE MARROW
CELL CYCLE
CELL PROLIFERATION
IN VITRO
INFLAMMATION
INHIBITION
METASTASES
NEOPLASMS
PATHOGENESIS
PATIENTS
PHOSPHORYLATION
POLYMERASE CHAIN REACTION
PROTEINS