Expression of the gangliosides GM3, GD3 and GD2 in tissue sections of normal skin, naevi, primary and metastatic melanoma

Abstract

Expression of the gangliosides GM3, GD3 and GD2 was studied in tissue sections from 19 naevi, 29 primary and 83 metastatic melanoma using the ABC immunoperoxidase technique. GM3 was not detected in normal skin whereas GD2 was detected on the basal and stratum spinosum of the epidermis and on peripheral nerves in the dermis. GD3 was expressed on melanocytes but not on most other components of normal skin. However, GD3 was strongly expressed on epidermis adjacent to naevi and primary melanoma whereas GD2, in contrast to that in normal skin, was not expressed on the epidermis adjacent to 26/29 primary melanoma. All naevi were positive for GM3 and GD3 except that GM3 was not detected on junctional components of naevi. GD2 was not expressed on naevi except in areas showing neuroid differentiation. Studies on melanoma revealed that approximately 60% of primary and 75% of metastatic melanoma expressed GM3 to a varying extent. With 2 exceptions, all primary and metastatic melanomas expressed GD3 although there was variable expression within most of the individual tumours. GD2 was detected in only approximately 25% of primary and 50% of metastatic melanomas. Both GD2 and GD3 were detected on lymphocytes surrounding melanoma. The higher expression of GD2 on metastases compared to primary melanomas was consistent with the view that GD2 expression was associated with increased metastatic potential. However, the low proportion of metastases expressing GD2 and the absence of any correlation with thickness of the primary tumour suggested that GD2 expression was not a reliable marker of metastatic potential. No differences could be detected in ganglioside expression on metastases in skin or lymph nodes. These results appear to have implications for the use of MAbs against gangliosides in therapy of melanoma and in the study of melanocytic differentiation.

Recombinant Human Hexamer-Dominant IgM Monoclonal Antibody to Ganglioside GM3 for Treatment of Melanoma

“…GM3 is the most common ganglioside found on human melanoma cells, where it is expressed at much higher densities and frequencies than on normal cells (14). Previously, several human IgM class antibodies were obtained from EBVtransformed human B cells (15,16).…”

Potentiation of interleukin-2 production and its binding by monoclonal antibodies to the gangliosides GD3 and GD2

“…The ability of mAbs to GD2 and GD3 to potentiate IL-2 production and to "up-regulate" IL-2-induced proliferative responses of lymphocytes suggests they may be valuable immunopotentiating agents. Their value in the role is further enhanced by their specificity for activated lymphocytes and the demonstration, in studies reported elsewhere [15,21], that lymphocytes expressing gangliosides GD2 and GD3 are located within and around metastatic and primary melanoma.…”

“…IgG concentrations in the supernatants of C281 and 14.18 were approximately 5-10 p~g/ml. C281 supernatant had a titer on melanoma tissue sections using avidin/biotin/immunoperoxidase techniques [18,21] of 1 : 4 (approximately 2.5 ~tg/ ml). C281 ascites had titers of approximately 1:200 (end titers taken as final dilution giving reactivity on sections).…”

Role of cell surface GM3 ganglioside and sialic acid in the antitumor activity of a GM3-based vaccine in the murine B16 melanoma model

“…GM3 is a monosialoganglioside, being the most abundant membrane glycolipid in melanoma cells (Hersey et al 1998;Nakakuma et al 1992). Previously, we have demonstrated that a GM3-based vaccine induced tumor protection in mice challenged with melanoma cells (Carr et al 2001;Alonso et al 1999).…”