Astrocytic tumours are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma. Various
neuropeptides, including
gastrin, are able to modulate tumour astrocyte migration. While
neurotensin has been shown to influence the proliferation of
glioma cells and the migratory ability of a large set of other cell types, its role in
glioma cell migration has never been investigated.
Neurotensin-induced modifications to the motility features of human U373
glioblastoma cells therefore constitute the topic of the present study. We evidenced that three subtypes of
neurotensin receptors (NTR1, NTR2 and NTR3) are expressed in U373
glioblastoma cells, at least as far as their mRNAs are concerned. Treating U373 tumour cells with 10 nM
neurotensin markedly modified the morphological patterns of these cells and also profoundly altered the organization of their actin cytoskeletons. Pull-down assays revealed that
neurotensin induced the activation in U373 cells of both Rac1 and Cdc42 but not RhoA. Scratch
wound assays evidenced that
neurotensin (0.1 and 10 nM) very significantly inhibited
wound colonization by U373 cells cultured in the absence of serum. In addition, quantitative phase-contrast videomicroscopy analyses showed that
neurotensin decreases the motility levels of U373
glioblastoma cells when these cells are cultured on
plastic. In sharp contrast,
neurotensin stimulates the motility of U373 cells when they are cultured on
laminin, which is a pro-adhesive extracellular matrix component ubiquitously secreted by
glioma cells. Our data thus strongly suggest that, in addition to
gastrin,
neurotensin is a
neuropeptide capable of modulating tumour astrocyte migration into the brain parenchyma.