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

Abstract

This work describes the in vivo expression and distribution of glioma-associated gangliosides (GD3, GM2, 3'-isoLM1) in a novel human brain tumour nude rat xenograft model. In this model, the tumours, which are established directly from human glioblastoma biopsies, show extensive infiltrative growth within the rat brain. This model therefore provides an opportunity to study ganglioside expression not only within the macroscopic tumour, but also in brain areas with tumour cell infiltration. The ganglioside expression was studied by confocal microscopy of immunostained brain sections using antiganglioside monoclonal antibodies. Xenografts from four human glioblastoma multiformes were established in rats and the brains removed after 3-4 months. Ganglioside GD3 was expressed in the tumour parenchyma while ganglioside 3'-isoLM1 was more abundantly expressed in the periphery of the tumour associated with areas of tumour cell invasion. GM2 expression was only seen in one tumour, where it was located within the main tumour mass. Double staining with a pan antihuman monoclonal antibody (3B4) and the antiganglioside monoclonal antibodies confirmed that the ganglioside expression was associated with tumour cells. This work supports the concept of different biological roles for individual gangliosides and indicates that antibodies or ligands directed against GD3 and 3'-isoLM1 might be complementary when applied in the treatment of human glioblastomas.

Glycosphingolipid Antigens in Neural Tumor Cell Lines and Anti-Glycosphingolipid Antibodies in Sera of Patients with Neural Tumors

“…In this study, we demonstrated that all tumor cell lines also expressed GD3 ganglioside, in addition to SGGLs. It is not surprising that GD3 could be a major surface marker of tumors, especially in neural tumors, such as melanoma [42,43] , brain tumors [44] , astrocytoma [45,46] , glioma [47] , neuroblastoma [48] , meningioma [49,50] , and intracranial tumors [51] . Serum antibodies against GD3 or OAc-GD3 have been shown to be elevated in some patients with melanoma [52] .…”

Mass Spectrometry for Cancer Biomarkers

“…Together with the immunochemical and immunohistochemical methods, several other biophysical techniques were introduced over the years for mapping and structural analysis of GGs in different gliomas, such as HPLC, infrared spectroscopy, and confocal microscopy via anti-GG monoclonal antibodies [112][113][114]. Additionally, the implementation of miniaturized, integrated devices for sample infusion into MS simplified the laborious chemical and biochemical MS strategies by reducing sample handling and sample loss, eliminating potential cross-contamination, and increasing ionization efficiency and quality of spectra as well as the possibility to perform unattended, high-throughput experiments [115].…”

Challenges for Therapeutic Application of Pseudomonas Exotoxin-Based Immunotoxins

“…Gangliosides are a group of sialic acid-containing glycosphingolipids with extending extracellular section. They are overxpressed in over 60 % of glioblastomas, making them attractive therapeutic targets for brain malignancies [131]. Piao et al developed a novel RIT, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT) that specifically binds these gangliosides.…”