Gangliosides modulate proliferation, migration, and invasiveness of human brain tumor cells in vitro.
Gliomas, the most common form of intrinsic brain tumor, are characterized by diffuse local invasion of the normal brain structures, irrespective of their histological grade of malignancy; a feature that is a major obstacle to successful therapy. They generally infiltrate the central nervous system (CNS) as individual tumor cells several centimeters beyond the macroscopic tumor margin and consequently often recur, after subtotal surgical resection. Factors involved in the control of both their proliferation and invasiveness are poorly documented. In this work, the role of gangliosides on proliferation of both human fetal human brain cells and five cell lines derived from human gliomas with different grades of malignancy was investigated. In addition, 8 microns-porosity polycarbonate filters were used to study cell motility. In addition, these filters were coated with the reconstituted extracellular matrix (ECM) composite, Matrigel, to assess invasiveness. The results presented show that gangliosides generally exert a proliferation inhibitory effect on fetal brain cells and glioma cell lines in vitro and play 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.
Merzak
A
A
Department of Neuropathology, Institute of Psychiatry, London, UK.
Koochekpour
S
S
McCrea
S
S
Roxanis
Y
Y
Pilkington
G J
GJ
D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003864:Depression, Chemical; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D005732:Gangliosides / Q000494:pharmacology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D014407:Tumor Cells, Cultured
D005732:Gangliosides