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Epidermal growth factor up-regulates CD44-dependent astrocytoma invasion in vitro

Authors

  • Monica Monaghan,

    1. Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, Belfast City Hospital Tower, Lisburn Road, Belfast BT9 7AB, UK
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  • Karl A. Mulligan,

    1. Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, Belfast City Hospital Tower, Lisburn Road, Belfast BT9 7AB, UK
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  • Heather Gillespie,

    1. Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, Belfast City Hospital Tower, Lisburn Road, Belfast BT9 7AB, UK
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  • Anne Trimble,

    1. Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, Belfast City Hospital Tower, Lisburn Road, Belfast BT9 7AB, UK
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  • Paul Winter,

    1. Department of Haematology, Royal Victoria Hospital, Belfast BT12 6BL, UK
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  • Patrick G. Johnston,

    1. Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, Belfast City Hospital Tower, Lisburn Road, Belfast BT9 7AB, UK
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  • Derek McCormick

    Corresponding author
    1. Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, Belfast City Hospital Tower, Lisburn Road, Belfast BT9 7AB, UK
    • Department of Oncology, University Floor, Belfast City Hospital, Lisburn Road, Belfast BT12 6BL, UK.
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Abstract

CD44/hyaluronan interactions and epidermal growth factor (EGF) stimulation are both known to enhance tumour invasion in vitro. The frequent amplification of the EGF receptor (EGFR) in high-grade astrocytomas led to the examination of the hypothesis that CD44-dependent astrocytoma invasion is regulated by EGF. It has been shown that human astrocytoma cells express only the standard (haemopoietic) form of CD44 (CD44s) and that EGF up-regulates CD44 mRNA and protein in a time- and dose-dependent (10–100 ng/ml) manner. EGF stimulation did not result in induction of additional splice variants. No EGF-induced increase in CD44s was observed after treatment of cells with the wild-type EGFR tyrosine kinase inhibitor Tyrphostin AG1478 (30 nM). Up-regulation of CD44 by EGF is also prevented by the transcriptional inhibitor actinomycin D (5 µg/ml) and by blocking the MAP kinase (MAPK) pathway using the MEK inibitor U0126 (100 µM). CD44 up-regulation was associated with a 50% increase in invasion through hyaluronan-supplemented Matrigel, which was abrogated by ligating CD44 with the specific antibody KM201. These results suggest that increased CD44 expression in response to EGF stimulation plays a significant role in astrocytoma invasion. Copyright © 2000 John Wiley & Sons, Ltd.

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