The presence of foetal ganglioside antigens 3′-IsoLM1 and 3′6′-IsoLD1 in both glioma tissue and surrounding areas from human brain

Abstract

Glioma-associated gangliosides, in particular the expression of foetal gangliosides 3'-isoLM1 and 3'6'-isoLD1, have been investigated in biopsies from 44 patients with astrocytoma grade II, anaplastic astrocytoma, anaplastic oligodendrogliomas, oligodendrogliomas, and glioblastoma multiforme. The total ganglioside content decreased in proportion to the estimated number of tumour cells present in the biopsy. Ganglioside GD3 was increased in 17 of the tumour tissues and in 6 of the surrounding area specimens. In agreement with our previous studies, tumour specimens contained the lactoseries ganglioside 3'-isoLM1 and, as demonstrated for the first time, the disialylated form of the ganglioside, 3'6'-isoLD1. These gangliosides are in normal brain tissue restricted to the developmental period. Most frequent was the expression of ganglioside 3'-isoLM1 which was detected in 92% of the tumour specimens in concentrations varying between just detectable amounts to 13 nmol/g wet weight. In the area surrounding the macroscopic tumour tissue 78% of the specimens expressed 3'-isoLM1 and the values varied between just detectable amounts to 24 nmol/g wet weight. Ganglioside 3'6'-isoLD1 was found in 47% of the tumour biopsies and in only 17% of the specimens taken outside macroscopic tumour tissue. The values varied between non-detectable amounts to 40 nmol/g wet weight of tissue. The expression of 3'-isoLM1 correlated significantly (p < 0.01) to malignancy grade. For 3'6'-isoLD1 a significant (p < 0.05) difference was found between tumour and surrounding tissue. Likewise, 3'6'-isoLD1 correlated significantly (p < 0.05) to malignancy grade. The correlation between 3'-isoLM1 and 3'6'-isoLD1 to malignancy grade and the frequent expression of these gangliosides both in the tumour itself and in its surrounding area should encourage additional studies concerning their biological role in tumour disease.

Tenascin‐R interferes with integrin‐dependent oligodendrocyte precursor cell adhesion by a ganglioside‐mediated signalling mechanism

“…1988 ; Paulus et al . 1993 ; von Holst et al . 1997 ), has been suggested to facilitate tumour growth and progression.…”

Tenascin-C inhibits 1 integrin-dependent cell adhesion and neurite outgrowth on fibronectin by a disialoganglioside-mediated signaling mechanism

“…Human neuroblastoma, glioma, and highly metastatic cells, such as melanoma and breast carcinoma cells, express considerable amounts of disialogangliosides (GD2, GD3, or their derivatives) involved in integrin-mediated adhesion of these cells to the ECM Cheresh et al, 1987;Burns et al, 1988;Marquina et al, 1996;von Holst et al, 1997). The disialoganglioside-dependent mechanism described by us is of particular importance in the light of the observations that (1) the degree of TN-C-induced inhibition of cell adhesion, i.e., increased cell motility, is proportional to the cell surface levels of disialoganglioside expression (the present study) and (2) melanoma cells deficient in GD3 ganglioside expression exhibit slower growth rates and lower tumorigenicity (Nakano et al, 1996) implying a crucial role for TN-C or related ECM proteins in the control of cell-matrix interactions during tumor metastasis.…”

The glioma‐associated gangliosides 3′‐isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains

“…One group of potential molecular targets are gangliosides, which are frequently differentially expressed in tumours [21,41,46], including gliomas [13,36,51,57]. It has also been shown that the expression of specific gangliosides is reflected in the malignancy grade of the tumour [3,14,47,52,58]. Furthermore, human monoclonal antibodies (MAbs) to several ganglioside antigens, such as GM2, GD2, GD3 and GM3, have been explored in melanoma therapy [1].…”

“…Previous studies have also shown that the ganglioside expression not only varies between different gliomas [17,22], but also between cells within the tumour [52], with cells in the periphery expressing different gangliosides than in the central parts. It has also been shown that the tumour cells change their ganglioside expression depending on the microenvironment in which they grow.…”

“…For example, the human glioma D54MG cell line [19,54] expresses high concentrations of ganglioside GM2 in vitro but when grown in vivo as subcutaneous xenografts in nude mice, a shift from GM2 to 3′‐isoLM1 and 3′6′‐isoLD1 expression has been observed [18,39]. Biochemical analyses have previously shown that the ganglioside 3′‐isoLM1 is upregulated in tissue specimens taken from the periphery of human gliomas [52]. Moreover, studies on post‐mortem brains from individuals with diagnosed gliomas have revealed that brain areas invaded by tumour cells contain relatively large amounts of 3′‐isoLM1 [17].…”