CXCL
chemokines display important roles in
glioblastoma (GBM) biology, including cell proliferation, death and migration features. While
temozolomide (TMZ) represents the standard chemotherapeutic used to treat GBM patients, its role in CXCL networking in GBMs remains unexplored. The effects of short-term and long-term in vitro treatment with
temozolomide on CXCL
chemokine expression were characterized in human
malignant glioma cell lines. U373 and T98G
astroglioma and Hs683
oligodendroglioma cells were cultured for months in the presence of increasing concentrations of TMZ (up to 1 mM), and their whole genome profiles were analyzed along with a complete mapping of all CXCL
chemokines and their respective receptor mRNAs. The study was extended to an additional established cell line and four primocultures. The in vitro results were compared with a clinical series of 156 human
gliomas and 23 normal brain tissue samples. The expression and secretion of CXCL2, CXCL3 and CXCL8 following different TMZ treatments were determined in Hs683, U373 and T98G
glioma cells. The long-term TMZ-treated
astroglioma cells, but not the Hs683
oligodendroglioma cells, developed in vivo a certain level of resistance to TMZ, which correlated with the up- regulation of CXCL2, CXCL3 and CXCL8 expression in the U373 and T98G
astroglioma cells. The transient down-regulation of CXCL2 in Hs683
glioma cells using
siRNA markedly impaired their proliferation rate. In conclusion, TMZ affects the expression and secretion of CXCL2 (and, to a lesser extent, CXCL3 and CXCL8) in
glioma cells, and CXCL2 directly impacts
glioma cell biology.