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Influence of host cell infiltration on the glycolipid content of mouse brain tumors
T N Seyfried1, M el-Abbadi, J A Ecsedy
1Department of Biology, Boston College, Chestnut Hill, Massachusetts 02167, USA.
Abstract:
Previous studies showed that levels of some glycosphingolipids (GSLs) expressed in solid brain tumors grown in vivo were reduced or undetectable in cultured cells prepared from the tumors. This phenomenon has been attributed either to suppressed glycolipid synthesis from unknown forces of the tissue culture environment or to the absence of host cells that normally infiltrate the solid tumors growing in vivo. To test further the host cell hypothesis, we examined host cell markers in two experimental mouse brain tumors, the ependymoblastoma and the CT-2A, that were grown as subcutaneous solid tumors in the flank of C57BL/6J (B6) mice or as cultured cells in vitro. The markers included ganglioside N-glycolylneuraminic acid (NeuGc), GA1 (asialo-GM1), and Fc receptor-bearing cells. NeuGc-containing gangliosides, GA1, and Fc receptors are expressed by macrophages and lymphoid-type cells of the mouse host immune system but are not normally expressed by mouse neural cells. Differences in the relative content of Fc receptor-bearing cells in ependymoblastoma and CT-2A tumors grown in vivo (8.3 and 16.8%, respectively) were proportional to differences in the relative content of NeuGc-containing gangliosides (25.5 and 45.1%) and GA1 (8.5 and 13.8%), respectively. Neither cultured tumor cell line expressed Fc receptors, GA1, or NeuGc-containing gangliosides. These findings suggest that non-neoplastic host infiltrating cells (macrophages) contribute significantly to the GSL composition of solid tumors growing in vivo.
Insights
Host immune cells, specifically macrophages, significantly influence the glycosphingolipid (GSL) composition of solid brain tumors. These infiltrating cells contribute GSLs not normally found in cultured tumor cells, explaining differences observed in vivo.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Glycosphingolipids (GSLs) are often reduced in cultured brain tumor cells compared to in vivo tumors.
- This reduction is hypothesized to be due to suppressed GSL synthesis or the absence of host immune cells.
Purpose of the Study:
- To investigate the role of host infiltrating cells in the GSL composition of experimental mouse brain tumors.
- To test the hypothesis that host cells contribute to GSLs in vivo.
Main Methods:
- Examined host cell markers (N-glycolylneuraminic acid (NeuGc), GA1, Fc receptors) in ependymoblastoma and CT-2A mouse brain tumors grown in vivo and in vitro.
- Assessed the presence of these markers in relation to tumor growth conditions.
Main Results:
- In vivo tumors showed significant levels of Fc receptor-bearing cells, NeuGc-containing gangliosides, and GA1, which were absent in cultured cells.
- The levels of these markers in vivo were proportional between the two tumor types, correlating with Fc receptor expression.
- Cultured tumor cell lines lacked Fc receptors, GA1, and NeuGc-containing gangliosides.
Conclusions:
- Non-neoplastic host infiltrating cells, primarily macrophages, significantly contribute to the GSL composition of solid brain tumors.
- The presence of host immune cells explains the altered GSL profiles observed in tumors grown in vivo compared to in vitro cultures.