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

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.