糖脂質と脳腫瘍—糖脂質組成とその分解酵素とくにlysosome酵素

GLYCOLIPIDS IN HUMAN BRAIN TUMORS:GLYCOLIPID COMPOSITIONS AND LYSOSOMAL ENZYMES

抄録　各種脳腫瘍におけるシアル酸量・ganglioside組成・中性糖脂質組成および各種lysosome酵素活性を測定した。シアル酸量は一般に正常脳に比較して腫瘍では低値を示し，特に転移性腫瘍で低かった。ganglioside組成は悪性gliomaほどGD₃の割合が高く，また，シアル酸を多く含むgangliosideの比率の低下を認めた。これは糖鎖不全現象を表わしていると思われた。また，GD_1a・N-acetylgalactosarnineが悪性gliomaで認められた。中性糖脂質組成は，gliomaではcerebrosideやsulfatideは高値であるが，悪性化するにしたがい，これらは低下していた。meningiornaではsulfatideはほとんど認めなかった。なお，cerebrosideの含有糖を測定したところ，gliomaではgalactoseがほとんどであるが，悪性gliomaほどgalactoseの割合が減り，giucoseが多くなってきた。各種lysosomeは，悪性であるほどその活性値が高値であった。これら糖脂質組成の変化とこれらの分解酵素の一つであるlysosome酵素活性の変化は，共に腫瘍の悪性化に関与すると考えられた。（なおgangliosideの命名はSvennerholm^19）にしたがった。）

Malignant transformation is characterized by the uncontrolled proliferation of cells produced by changes in cell surface components such as glycolipids and glycoproteins. Changes in the components of glycosphingolipids on the cell surface may be involved in the intracellular adhe-sion of cell growth and accompany malignant transformation of cells.

In the present report, ganglioside as well as neutral glycosphingolipid compositions were stu-died in various neural tumors and abnormal gangliosides associated with malignant transforma-tion were found. Simultaneously, various lysosomal enzyme activities, which may be partly responsible for the catabolism of glycolipids, were also mea-sured. Ganglioside and neutral glycosphingolipid compositions in various brain tumors were analyz-ed by Porch method, thin-layer chromatography, gas chromatography and densitometer.

In glioma, GD 3 was a major form and was found in all gangliosides. Malignant glioma espe-cially contained a higher proportion of GD 3. Increases in GD 1 a-gal NAc were found in high grade glioma, a finding which appears to be uni-que. This ganglioside increased in brain affected by Tay-Sachs disease but was not present in normal brain and low grade gliomas. Generally, high grade gliomas showed increased disialogan-gliosides and decreased trisialogangliosides as compared with low grade gliomas.

In meningioma, the meningotheliomatous type contained higher proportions of GM 3 and GD la, but the fibroblastic type contained only GD 3.

Neutral glycosphingolipids in glioma and me-ningioma also differed among each type of tumor and varied according to the degree of glioma malignancy.

Lysosomal enzyme activities, which included α-galactosidase, β-galactosidase, a-mannosidase, β-hexosaminidase and arylusulphatase A, main-tained very high activity in malignant gliomas and metastatic tumors.

These findings will not only benefit clinical diagnosis, but will also provide greater under-standing of the biochemical characterization of brain tumors and the functional importance of gangliosides and neutral glycosphingolipids. In addition, the activity of lysosomal enzymes in malignant tumors might be related to the malig-nant formation of tumors. Lysosomal enzymes play a role in the catabolism of glycolipids. These changes in ganglioside and neutral glycosphingo-lipid composition, and the high activity of lysoso-mal enzymes would seem to be related to malig-nant changes in tumors.