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The Gade Institute, Department of Pathology, University of Bergen, N-5021 Bergen, Norway [O. E., R. B.], and The Brain Tumor Research Center, University of California, San Francisco, San Francisco, California [M. E. B.]
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 µM 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 µM 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 µM ALP.
ALP caused a dose-dependent inhibition of invasion by GaMg tumor spheroids into brain aggregates. After 168 h of 1.0 µM 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.
1 O. E. and R. B. were supported by The Norwegian Cancer Society, Grants 88218 and 89002. M. E. B. was supported by a grant from the Preuss Foundation.
2 To whom requests for reprints should be addressed, at The Gade Institute, Department of Pathology, University of Bergen, Haukeland Hospital, N-5021 Bergen, Norway.
3 Current address: Laboratory of Neuro-Oncology Research, Barrow Neurological Institute, 350 West Thomas Road, Phoenix, AZ 85013-4496.
Received 9/25/90. Accepted 1/ 7/91.
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