Effect of alkyl-lysophospholipid on glioblastoma cell invasion into fetal rat brain tissue in vitro.
The antitumor effect of alkyl-lysophospholipid (ALP) was studied on a continuous glioma cell line (GaMg) as well as on tumor spheroids obtained from three different primary brain tumor biopsies. GaMg monolayer growth was reduced by 50% after treatment with 30 microM ALP; cells accumulated in the G2M phase of the cell cycle as determined by flow-cytometric analyses. Tumor spheroid growth was reduced by 25 and 44% during treatment with 10 and 30 microM ALP, respectively. These drug concentrations also caused a severe destruction of spheroids. No effect on growth or morphology was seen in spheroids treated with 0.1 and 1.0 microM ALP. ALP caused a dose-dependent inhibition of invasion by GaMg tumor spheroids into brain aggregates. After 168 h of 1.0 microM ALP treatment, the volume of the intact brain aggregate was 90% larger than that in the untreated co-cultures. To further investigate the efficacy of ALP as an anti-invasive drug, co-cultures were performed with specimens obtained from three primary brain tumors: a highly invasive glioblastoma multiforme, an anaplastic astrocytoma, and an astrocytoma. Treatment of spheroids from the most invasive tumor with ALP caused a 7-fold preservation of normal brain tissue relative to control co-cultures. Moreover, the sensitivity of primary glioma spheroids to the anti-invasive effect of ALP seemed to be associated with the aggressiveness of the tumor; spheroids from the more malignant specimen (glioblastoma multiforme) were more sensitive than those from the less aggressive tumors. The anti-invasive effect seen with nontoxic concentrations of ALP may prove valuable in the treatment of malignant gliomas.
Engebraaten
O
O
Gade Institute, Department of Pathology, University of Bergen, Norway.
Bjerkvig
R
R
Berens
M E
ME
D000328:Adult; D000818:Animals; D001921:Brain / Q000473:pathology*; D002241:Carbohydrates / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D051381:Rats; D014407:Tumor Cells, Cultured
D002241:Carbohydrates; D008246:Lysophospholipids