Lactotetraose series ganglioside 3',6'-isoLD1 in tumors of central nervous and other systems in vitro and in vivo.
Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuAc or NeuGc)alpha 2-6GlcNAc. The distribution of 3',6'-isoLD1 in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoLD1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV3NeuAcLcOse4Cer in vitro, expressed detectable levels. Expression of 3',6'-isoLD1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoLD1. The absence of 3',6'-isoLD1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoLD1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoLD1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoLD1 expression within the human central nervous system to periods of fetal-neonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.
Wikstrand
C J
CJ
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Longee
D C
DC
McLendon
R E
RE
Fuller
G N
GN
Friedman
H S
HS
Fredman
P
P
Svennerholm
L
L
Bigner
D D
DD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000918:Antibody Specificity; D002240:Carbohydrate Sequence; D016543:Central Nervous System Neoplasms / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005732:Gangliosides / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000032:analysis*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D009844:Oligosaccharides; C078813:IV(3)-NeuAc-LcOse4Cer; C078812:IV(3)-NeuAc-III(6)-NeuAc-LcOse4Cer; C013084:lacto-N-neotetraose