Chemokines participate in cellular processes associated with
tumor proliferation, migration, and angiogenesis. We previously demonstrated that
stromal cell-derived factor 1 (SDF1) exerts a mitogenic activity in
glioblastomas through the activation of its
receptor CXCR4. Here we studied the expression of this
chemokine in human
meningiomas and its possible role in cell proliferation.
Reverse transcriptase-PCR analysis for CXCR4 and SDF1 was performed on 55 human
meningiomas (47 WHO grade I, 5 WHO II, and 3 WHO III). Immunolabeling for CXCR4 and SDF1 was performed on
paraffin-embedded sections of these
tumors. [(3)H]
Thymidine uptake and Western blot analyses were performed on primary meningeal cell cultures of
tumors to evaluate the proliferative activity of human SDF1alpha (hSDF1alpha) in vitro and the involvement of
extracellular signal-regulated kinase 1/2 (ERK1/2) activation in this process. CXCR4
mRNA was expressed by 78% of the
tumor specimens and SDF1
mRNA by 53%. CXCR4 and SDF1 were often detected in the same
tumor tissues and colocalized with
epithelial membrane antigen immunostaining. In 9 of 12 primary cultures from
meningiomas, hSDF1alpha induced significant cell proliferation that was strongly reduced by the
mitogen-activated protein kinase kinase inhibitor
PD98059, involving ERK1/2 activation in the proliferative signal of hSDF1alpha. In fact, CXCR4 stimulation led to ERK1/2 phosphorylation/activation. In addition, the hSDF1alpha-induced cell proliferation was significantly correlated with the MIB1 staining index in the corresponding surgical specimen. In conclusion, we found that human
meningiomas express CXCR4 and SDF1 and that hSDF1alpha induces proliferation in primary
meningioma cell cultures through the activation of ERK1/2.