グリオーマ細胞におけるガングリオシドGM_3の細胞浸潤における役割
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概要
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We studied the mechanism of invasive ability of glioma cells with a special interest in the role of ganglioside GM3, of which biological role is still uncertain. The glioma cell line used was RG2, which contains GM3 as its sole ganglioside. We performed in vitro assay by using a filter coated with a reconstituted basement membrane (Matrigel). The number of invading RG2 cells through the Matrigel was increased by 45.5% by depleting GM3 from the cells with D-PBPP (an inhibitor of ganglioside synthesis), which could be returned to the pretreatment level by adding GM3 to the cells. Zymography revealed that D-PBPP treatment did not influence the metalloproteinase activity, which was thought to play an important role in determining the capability of glioma cell invasion. Above results strongly indicate that GM3 functions in cell invasion. Immunohistochemistry revealed GM3 to be located on the cell membrane particularly at the foot processes of the cells. Since GM3 has only the sphingolipid portion of its stucture within the cell membrane, we speculated upon its function in invasion was mediated with certain membrane proteins. We examined the possible association with integrins, which was found to co-localize with GM3 at the focal adhesion plaques of RG2 cells. The invasive ability of RG2 cells was modulated by antibodies to integrins; antibodies to alpha3-, alpha4-, and alpha5-integrin chains suppressed the number of invading cells from 3.1% to 36.4%, and an antibody to betal chain markedly increased its number by 36.4%. Although there was no direct evidence to suggest that GM3 and integrins actually cooperate in the invasion of RG2 cells at present, their common location at the focal adhesion plaques suggested that GM3 may function with integrins in the process of cell invasion.
- 2000-04-01