GANGLIOSIDES MODULATE PROLIFERATION, MIGRATION, AND INVASIVENESS OF HUMAN BRAIN-TUMOR CELLS IN-VITRO

Gliomas, the most common form of intrinsic brain tumor, are characteri zed by diffuse local invasion of the normal brain structures, irrespec tive of their histological grade of malignancy; a feature that is a ma jor obstacle to successful therapy. They generally infiltrate the cent ral nervous system (CNS) as individual tumor cells several centimeters beyond the macroscopic tumor margin and consequently often recur, aft er subtotal surgical resection. Factors involved in the control of bot h their proliferation and invasiveness are poorly documented. In this work, the role of gangliosides on proliferation of both human fetal hu man brain cells and five cell lines derived from human gliomas with di fferent grades of malignancy was investigated. In addition, 8 mu m-por osity polycarbonate filters were used to study cell motility. In addit ion, these filters were coated with the reconstituted extracellular ma trix (ECM) composite, Matrigel, to assess invasiveness. The results pr esented show that gangliosides generally exert a proliferation inhibit ory effect on fetal brain cells and glioma cell lines in vitro and pla y an important role in promoting glioma cell motility and invasiveness . The molecular mechanisms involved in the action of gangliosides may prove useful in identifying new targets for an anti-invasion therapy.